DNAFit’s DNA test falls into the category of SNP analysis, which is a form of genotyping. Read more about what a SNP analysis entails in our article, The difference between unlocking your full genome and a SNP analysis.
As part of DNAFit’s desire to not only present you with genetic information, but also to educate you about the genes that we analyse, we are going to look at a specific gene in detail, see what the science says about it, and how it can affect you with regards to fitness and diet.
The first gene to be put under the microscope is ACE, or the angiotensin-converting enzyme gene. ACE is a special gene because it appears in three different sections of the DNAFit reports – power/endurance profile, carbohydrate sensitivity, and salt sensitivity. This gene is reported to slightly differently to most other genes too, in as much as you can have the Insertion (or I) allele, or the deletion (D) allele. The main function of angiotensin-converting enzyme is to convert angiotensin-I to angiotensin-II. Those with the DD genotype tend to have more of the ACE enzyme, and so generally are more effective at converting angiotensin-I to angiotensin-II.
ACE was the first gene to be linked to human performance. In a 1998 paper, researchers got military recruits to do bicep curls with a 15kg barbell, both before and after basic military training. What they found was that after training, those with the I allele (II or ID genotypes) saw improvements in how long they could carry out these bicep curls for, whilst those with the DD genotype did not. This enabled the researchers to predict that the I allele was associated with greater improvements to endurance training, and the D allele associated with greater improvements from higher intensity training. Research has also shown that those with the II genotype tend to have more slow twitch muscle fibres, and those with the DD genotype tend to have a greater number of fast twitch muscle fibres (you can read more on slow and fast twitch muscle fibres here.
ACE has also been found to affect sensitivity to carbohydrates. Individuals with the DD genotype are more likely to suffer from lower insulin sensitivity, which in turn can increase the risk of developing type II diabetes. In a study from 2009 in Czech adults, when daily carbohydrate intake was high, those with the DD genotype were much more likely to be obese compared to the II genotype. This suggests that those with the DD genotype tolerate carbohydrate less well compared to those with the II genotype, and so as a result should consume fewer refined carbohydrates, and also aim for a lower total glycaemic load per day.
ACE also plays a role in blood pressure control, and so has been implicated in the development if salt sensitive hypertension, or high blood pressure with high salt intake. In a group of studies, it was repeatedly shown that those with the II genotype of ACE were more sensitive to salt with regards to hypertension – that is if II genotypes consumed high amounts of salt, they were more likely to suffer from hypertension. This effect was much lower in DD genotypes.
So what does all this mean to you? Well, knowing your ACE genotype can empower you to make better decisions regarding your training and also your diet. If you have the II genotypes, you are more likely to respond favourably to endurance-based training, be able to consume more carbohydrates, and you should also consume less salt on a daily basis. If you have the DD genotype, you are more likely to have a favourable response to power training, not have an increased risk of developing salt sensitive hypertension, and also limit carbohydrates more than II genotypes. ID genotypes would sit somewhere in between the two.
The next gene in this series is another one that appears in two separate sections – COL5A1. This gene is interesting because it can have an effect on endurance performance and also injury risk; but the allele that increases injury risk also improves endurance performance; one of nature’s cruel jokes.
The COL5A1 gene encodes for a protein that is part of type V collagen, one of the main constituents of ligaments and tendons, alongside type I collagen, in which COL1A1, another of our genes that we will meet later, encodes for. What research tells us is that people will have different alleles at a specific point in this gene, which can increase or decrease their risk of injury. A study from 2009, for example, showed that those with the CC genotype of COL5A1 had a significantly decreased risk of developing Achilles tendonitis compared to carriers of the T allele. Similar results have been found in regards to anterior cruciate ligament (ACL – a ligament found in the knee) injuries, again with CC genotypes being under-represented in a group of people suffering for an ACL injury. It has also been found that those with the T allele generally have a lower range of motion, which typically means that they are less flexible. Added to this, research has shown that those with the TT genotype have stiffer tendons than those with the CC genotype, potentially contributing to this decreased range of motion. It is thought that the stiffer tendons and a decreased range of motion might potentially increase injury risk, which is why T allele carriers are at a slightly higher risk of an injury.
So how does this affect endurance performance? Well, it turns out that stiff Achilles tendons tend to store and return energy better than less stiff ones, which means that in long distance running, less energy is required per step, making runners more efficient. As such, the T allele, because it increases tendon stiffness, is advantageous in long distance running events. This was shown in a 2011 study looking at an ultra-marathon event. It was found that those with the TT genotype, the type associated with stiffer tendons, were significantly faster in their finishing time than those with the CT and CC genotype.
What does all this mean for you? If you have a T allele, you may well respond better to endurance training, especially long distance running. You also potentially have a higher injury risk, especially compared to those with the CC genotype. Whilst this sounds like bad news, it really isn’t – being aware of this allows you to be proactive in terms of injury prevention. This might take the form of regular massage, or injury prevention techniques such as eccentric loading exercises, which have been shown to be very effective at reducing the risk and severity of symptoms of tendon injuries.
The next gene we are going to discuss is ACTN3. It’s one of the most well studied genes with regards to sporting performance. ACTN3 codes for a protein that is found exclusively in the fastest kind of muscle fibres, type IIx, called a-actinin-3. Fast twitch muscle fibers can contract quickly and powerfully, and as such are linked to sprinting or weightlifting. Generally, people who are quick or strong will have plenty of type-IIx muscle fibers, whilst people who are better at long distance running will have more type-I muscle fibers (often called slow twitch muscle fibers).
There are two different alleles for ACTN3; C & T. The C allele allows for correct production of the a-actinin-3 protein, and the T version prevents this protein from being made. Not being able to produce this protein does not cause any disease, as muscles can function without it, but it might limit the amount of fast twitch muscle fibre that can be produced. These two different alleles can create three different genotypes; CC, CT and TT.
It isn’t rare to have the TT genotype; roughly 18% of European Caucasians are TT, whilst up to 30% of Asians can have the TT genotype. In people of African descent, the T allele is rarer, and some research has reported that as little as 1% of certain African populations have the TT genotype.
The first studies on ACTN3 were association studies. In these studies, scientists tested a group of people who were not involved in high-level sport, and used them as a control group. They then tested elite sprinters, power athletes, and elite endurance athletes, to see if there were any differences between them. They found that elite speed and power athletes were much more likely to have the C allele in the form of either the CC or CT genotype than the control group. Generally, elite speed power athletes don’t have the TT genotype, as it occurs roughly 3% of these individuals, compared to about 18% of control groups. In fact, in one study no sprint Olympians had the TT genotype. In contrast to this, the studies found that elite endurance athletes were much more likely to have the TT genotype than the control groups.
So what does this mean for you? Your ACTN3 genotype can’t tell you whether you can be a world class sprinter or not, because there are cases of elite power athletes with the TT genotype. However, it can be used to indicate how you will respond to different training. What we know is that individuals with a C allele generally respond better to power training than individuals with the TT genotype. The reason for this is that the C allele allows you to grow type IIx muscle fibers from exercise. These muscles fibers respond really well to power and strength training, and tend to grow larger than other types of muscle. Another interesting study has shown people with the CC genotype have higher levels of testosterone than the TT genotype, with CT falling somewhere in the middle. Testosterone is an additional factor that determines how well someone can gain muscle, with more testosterone allowing more muscle mass to be built. This is part of the reason why men tend to grow muscle tissue more quickly than women, as men have much higher levels of testosterone than females.
In terms of training, research shows that those with a C allele generally see greater improvements in muscle strength and power following high intensity training, such as lifting heavy weights for a low number of repetitions. Having a TT genotype does not mean that you can’t get strong or grow your muscles, it means you just have to train in a way that suits your genetic profile a bit more. This will include doing weights for 12-15 repetitions, trying to take the muscle as close to failure as possible. Conversely, if you have the CC genotype, you should focus a bit more on lifting heavy weights for a lower number of repetitions, somewhere between 3 and 6. If you have the CT genotype, then a mix of both types of training should prove useful.
The next gene we’ll be looking at is CYP1A2. The enzyme produced by this gene is responsible for about 95% of all caffeine metabolisation in your body. This is why we include CYP1A2 in our caffeine report. It also plays a role in phase-1 detoxification, particularly in how well your body deals with HCAs and PAHs found in charred meats.
As with all our genes, there are two different CYP1A2 alleles, in this case A and C. The A allele is associated with a higher activity of the CYP1A2 enzyme, and the C allele is associated with lower activity of the enzyme.
Research on the effects of caffeine on cardiovascular health found that the effect of caffeine differs between genotypes. With regard to caffeine response, AA genotypes tend to metabolise caffeine quicker than AC and CC genotypes. As a result, AA genotypes are called “fast metabolisers” and the AC and CC genotypes are classed as “slow metabolisers”.
A 2006 study found that slow metabolisers who had more than about three cups of coffee per day, increased their risk of suffering from a myocardial infarction (heart attack). Fast metabolisers, however, didn’t see an increase in heart attack risk. The same is true for hypertension. A 2009 study found that higher amounts of caffeine (around 300mg per day) was associated with an increased risk of hypertension – but only in slow caffeine metabolisers. Based on these studies, and others like them, DNAFit recommends that slow metabolisers should limit their intake of caffeine to around 200mg per day. Fast metabolisers can consume more caffeine should they wish, up to approximately 300mg per day.
We also look at CYP1A2 from the perspective of phase-1 detoxification ability, which looks at how well your liver can handle two compounds found in cooked meats. These compounds are HCAs and PAHs which form when meat is cooked at a high temperature, and has become blackened, crispy, or chargrilled. When we eat this meat, our body starts to break down these HCAs and PAHs creating a toxic by-product.
If you breakdown these HCAs and PAHs quickly, you get a rapid increase in this toxic by-product which overwhelms your body. However, if you break them down slowly, you get a much gentler increase in the toxic by-product - lowering your risk of toxin build up.
CYP1A2 is one of the genes involved in this pathway, and A allele carriers are classed as fast metabolisers, with CC genotypes classed as slow metabolisers.
In the case of fast metabolisers, we recommend that they limit their consumption of grilled or smoked meats, and focus on protecting the meat during the cooking processes. This requires using a lower cooking temperature - so, cooking with a liquid (curries, stews, stir fries, marinades) should help with this.
As you can see, your version of the CYP1A2 gene can have an impact on how well you tolerate caffeine, and how well you process HCAs and PAHs. Both of these things can have a profound impact on your future health. By understanding your body on a genetic like this, you can make important dietary changes which can maximise your health both in the short and long term.
We are now going to look at a gene that affects our saturated fat sensitivity, called ApoA2. This gene creates Apolipoprotein A-II, which is part of high density lipoproteins (HDL). A small change in this gene can have an effect on how well you can transport cholesterol, and the research also indicates that it can have an impact on how well you can tolerate saturated fat.
A good example of a research paper which supports the impact of ApoA2 on saturated fat sensitivity comes from 2009. In this study, the researchers looked at 3,462 subjects, and asked them questions about their intake of food, and also measured their Body Mass Index (BMI), which is their weight in kilograms divided by the square of their height. What they found was that when saturated fat intake was low, there was no difference in BMI between ApoA2 genotypes.
However, when saturated fat intake was high, then a difference started to emerge. When the subjects consumed more that 22 grams of saturated fat per day, those with the CC genotype of ApoA2 gene had a significantly higher BMI than when they consumed less than 22 grams of saturated fat per day; this effect was not seen in TT or TC genotypes. As such, this study, and others like it, have enabled us to identify that the C allele of ApoA2 is associated with an increased likelihood of weight gain with high intakes of saturated fat.
If we know that CC genotypes are at an increased risk of weight gain with higher saturated fat sensitivities, then using that information can help us make simple dietary recommendations, which is that CC genotypes should typically consume lower amounts of saturated fat. In the DNAFit report, we look at 6 other single nucleotide polymorphisms (SNPs) which can affect how well you tolerate saturated fat, allowing us to give a good reflection of how sensitive you are to saturated fat. The higher your sensitivity, the less saturated fat we would recommend that you should consume.
Overall, ApoA2 is a gene that affects saturated fat sensitivity, such that CC genotypes should limit their intake to less than 22g of saturated fat per day, on average. It is one SNP in our panel, that, in conjunction with other SNPs, gives us a better idea of your overall saturated fat sensitivity.
The next gene is perhaps one of the more controversial ones; MTHFR. This gene creates an enzyme with an incredibly long name – Methylene tetrahydrofolate reductase. This enzyme is part of a complex chemical pathway known as the methyl cycle, which plays a role in the conversion of a potentially harmful compound called homocysteine, into a safe amino acid, called methionine.
There are two common single nucleotide polymorphisms, or SNPs, found in the MTHFR gene. These have the catchy names of C677T and A1298C. Currently, DNAFit only test for the C677T SNP, because this is the only SNP in MTHFR to meet our scientific criteria for inclusion. The A1298C SNP has been studied extensively, but so far no clear consensus is available as to whether it has a meaningful effect or not – if the evidence becomes clearer in time, then DNAFit will add A1298C to our testing panel, and report on it.
With regards to the C677T SNP that we test for, there are two different alleles, C and T, which create three different genotypes, CC, CT, and TT. The research has shown that your genotype for this SNP can impact how well your MTHFR enzyme works. In those with the CC genotype, the enzyme works very well. In the CT and TT genotypes, the enzyme significantly less efficient. And, if the enzyme doesn’t work quite as well, this means that you’re not as good at converting homocysteine to methionine, which means you are more likely to have a build-up of homocysteine in your blood. This is potentially problematic, as high levels of homocysteine have been linked to an increased risk of suffering from cardiovascular disease and hypertension.
However, the good news is that this risk is very easily reduced by just having slightly more B vitamins on a daily basis. Those with at least one copy of the T allele should focus on consuming more than the RDA of vitamin B6, B9 (folate), and B12.
The evidence is really good that T allele carriers are more likely to have higher levels of homocysteine, but by focusing on consuming more vitamin B9, their homocysteine levels can be significantly reduced.
A study from 2002 showed that at least 600ug of vitamin B9 should be consumed by T allele carriers to reduce their homocysteine, compared to the RDA of 400ug. As such, the recommended daily allowance of B9 is insufficient for the needs of T allele carriers, which is why in our report we would recommend a higher amount.
So where is the controversy? Some people, particularly in the USA, feel that SNPs in MTHFR are responsible for a host of other illnesses and diseases, which currently the evidence doesn’t really support. There is also a lot of controversy regarding the type of vitamin B9 that should be consumed. Vitamin B9 occurs naturally in foods as folate, and in supplements as folic acid. The vast majority of research into MTHFR shows that folic acid is effective at reducing homocysteine, without reports of side effects. The body of research looking at folic acid in general also supports the notion that low doses of the vitamin are safe. Again, some practitioners believe that folic acid is unsafe for those with the TT genotype of MTHFR, and would recommend a different supplement, called methylated folate (or 5MTHF). The evidence supporting the use of this supplement is limited, particularly when folic acid has repeatedly been shown to be effective in all MTHFR genotypes. We would recommend that everyone attempts to get their vitamin B9 from natural sources, such as green leafy vegetables. Should this evidence change in future, we would also change our recommendations to reflect that.
In conclusion, small changes in a person’s MTHFR gene can have an impact on their homocysteine levels. The RDA of B6, B9 and B12 is likely sufficient for CC genotypes, but T allele carriers should consume slightly higher amounts for all these vitamins, especially B9, with our recommendation being between 600-800ug per day, compared to the RDA of 400ug. This amount of B9 can be found in a cup each of spinach, asparagus, and broccoli, so all the more reason to load up on your greens!
Now we are going to be looking at a gene that affects how well we can tolerate lactose. Roughly 65% of the world’s population lose the ability to digest lactose, the sugar found in milk, after weaning. From an evolutionary perspective, this makes sense – humans typically need to digest milk when they are babies because their main source of nutrition is breast milk; however, once the child has stopped breast feeding, historically there was no need for them to continue to digest lactose, because milk wasn’t readily available.
However, as humans migrated out of Africa into Asia, and eventually into Europe, a small polymorphism occurred which enabled some of them to continue to digest lactose into adulthood. This was useful because it now meant that instead of killing their animals for meat, they could consume their milk, thus creating a renewable source of nutrition. This, in turn, allowed humans to migrate even longer distances, spreading into Northern Europe. Today, between 85-95% of Britons are lactose tolerant, compared with around 60-75% of Southern Europeans. The number of lactose tolerant individuals gets smaller as we move into Asia and Africa; in some places 100% of the population are lactose intolerant.
Lactose intolerance occurs when the body is unable to digest lactose, the sugar found in milk. Instead of being absorbed through the small intestine, the undigested lactose travels to the colon, where bacteria begin to break it down via fermentation. This process creates a lot of gas, which leads to the symptoms associated with lactose intolerance – bloating, stomach cramps, excessive gas, and diarrhoea. The main cause of lactose intolerance is called primary lactose intolerance; this is where the body doesn’t produce lactase, the enzyme that breaks down lactose. This is genetic, and determined by the LCT SNP C/T(-13910.
The LCT SNP has two alleles, C & T; the T allele is what gives people the ability to continue to produce lactase, the enzyme which digests lactose, into adulthood.
In summary, if you have a T allele, you have the ability to produce lactase, which means you should be able to tolerate milk products. Those without a T allele will likely have lost the ability to produce lactase, and as such will be unlikely to tolerate milk products. However, it’s worth pointing out that having at least one T allele doesn’t guarantee that you can tolerate milk products; this is because some people might have something called secondary lactose intolerance, which is not genetic, and is instead often caused by a bacterial infection, virus, or stomach injury/disease (such as coeliac disease). It’s also possible to be lactose tolerant, but have a cow’s milk protein allergy – although this affects less than 1% of people. The flipside of this is that even people with lactose intolerance can often consume small amounts of lactose without any symptoms. Nevertheless, knowing and understanding your LCT genotype can be important when it comes to seeing which foods you can tolerate, and explaining why you might experience certain symptoms with milk products.
The gene that we are going to be taking a closer look at is TCF7L2. This gene creates a protein called transcription factor 7-like 2, which in turn binds to other genes to alter their expression. It has been shown through research to have an impact on how well you tolerate carbohydrates, and how well you tolerate saturated fat, which is how we report on it in the DNAFit reports.
With regards to carbohydrates sensitivity, the TCF7L2 gene appears to play a role in the development of type-II diabetes, potentially through impairment on insulin sensitivity. Many studies have reported this association, including one by Cornelis et al., published in 2009. In this study, the researchers recruited just over 3,000 nurses from a much larger longitudinal study taking place in the USA, called the Nurses Health Study (NHS). Of these 3000 subjects, 1140 had developed type-II diabetes, and the rest had not.
As part of the NHS, which started in 1976 and recruited 121,700 female nurses, everyone involved was sent questionnaires every two years. These questionnaires often asked questions about food intake, and what the typical dietary habits of the nurses was like. From this, it was possible to find out not only how much fat, carbohydrate, and protein was typically consumed by these nurses, but also the type of each; of special interest to us in this case in the type of carbohydrate consumed – low Glycaemic Index (GI) or high GI. This allowed the researchers to see if there was an association with type of carbohydrates and the development of type-II diabetes, but also to see if this associated was enhanced or reduced by differences in the TCF7L2 gene.
What did they find? Firstly, a high-GI diet was found to be slightly more likely to cause the development of type-II diabetes than a low carbohydrate diet, which goes along with what we already know. However, when looking at TF7L2 genotype, this effect was much larger. Those nurses with two copies of the risk allele and following a diet with a high glycaemic index were 2.7 times more likely to develop type-II diabetes than those with no risk alleles. With a low-GI diet, this risk was significantly reduced. It makes sense, therefore, that those carrying a risk allele of TCF7L2 should consume a diet with an overall low GI, prioritising carbohydrates from fibrous vegetables over simple sugars and refined carbohydrates.
Other studies have shown that high saturated fat intake along with having at least one T allele increases the risk of having a reduction in insulin sensitivity.
The next gene is VDR; the vitamin D receptor gene. This gene plays a role in how well our bodies can utilise vitamin D, which in turn can affect various different processes. Currently, VDR appears in three different sections of our report – power/endurance, vitamin D needs, and caffeine sensitivity.
When we report on vitamin D requirements, we are doing so from the perspective of bone health. Changes in the VDR gene, known as polymorphisms, have been shown to have an impact on how strong and healthy our bones are. For example, a 2005 study found that the VDR CC genotype was associated with an increased risk of a hip fracture in a group of elderly post-menopausal women. If we know that someone is at an increased risk of developing a fracture of any type, then we can be proactive in preventing that. From a nutritional standpoint, both vitamin D and calcium work together to improve bone strength – as such, if we find that you have at least one C allele of VDR, we would recommend slightly higher intakes of these nutrients above the recommended daily allowance.
VDR genotype can also play a role in caffeine sensitivity. We have previously discussed CYP1A2 in this series, a gene that plays a very large role in determining how well you can tolerate caffeine, but we also need to pay attention to which version of the VDR gene we have. That’s because there is evidence that those with the CC genotype are more likely to see a loss of bone mineral density with high caffeine intakes. A loss of bone mineral density has also been linked to an increased risk of fractures, which we want to avoid. Due to this, if you have the VDR CC genotype, we would recommend that you limit your caffeine intake to less than 200mg per day, about as much found in 2-3 cups of coffee, depending on how strong you like your coffee.
Finally, VDR genotype can have an effect on whether you respond well to power-based training or not. Polymorphisms in this gene have been linked to differences in muscle strength and muscle. In this case, CC genotypes may achieve more favourable muscle growth and bone density improvements with strength training, as opposed to endurance training.
From a health perspective then, we can see that carrying a C allele means we need to be a little bit more prudent in ensuring we get enough vitamin D whilst reducing our caffeine intake. Vitamin D can be found primarily in oily fish, but also in eggs and some fortified dairy products. The sun is also a really great source of vitamin D. From a training perspective, C allele carriers are perhaps a bit more likely to have a better response to strength training.
GDF-5 is a gene which encodes for a protein called Growth Differentiation Factor-5. Whilst the specific role of this protein is currently unknown, we do know that a SNP contained within the gene is associated with an increased injury risk, especially with regards to tendons, ligaments, and bone.
One study which looked at this was published in 2010. In this study, researchers got a group of people who were suffering from an Achilles tendon injury, and a group who weren’t. What they found was that, within a group of the people with an Achilles tendon injury, the TT genotype of GDF-5 was significantly “over-represented”, meaning that it was more common than both the CC and CT genotypes. Further analysis from this paper lead the researchers to conclude that those people with the TT genotype of GDF-5 were about twice as likely to develop Achilles tendinopathy than C allele carriers. It is based on research like this, and similar papers, that we report that the T allele of GDF-5 is associated with an increased tendon and ligament injury.
We also look at GDF-5 from the perspective of bone health. Plenty of researchers have looked at this, and we will look at an example of one study from 2009. In this study, the scientists looked at over 6000 people, to see if there was any association between their GDF-5 genotype and their risk of developing osteoarthritis, a disease that affects joints, caused by the breakdown cartilage and bone, resulting in pain, and also their risk of suffering a bone fracture. They found that, in elderly women, those with the CC genotype of GDF-5 had just under a 40% less chance of developing osteoarthritis in their hands, and just over 30% less chance of developing it in their knees. They also had a 29% less chance of suffering from a fracture. This lead the researchers to conclude that CC genotypes were protected against both osteoarthritis and fracture risk.
What does all this mean for you? If you have a T allele, you potentially have a higher injury risk, especially compared to those with the CC genotype – both in terms of tendon injury, but also bone injury. Whilst this sounds like bad news, it really isn’t – being aware of this allows you to be proactive in terms of injury prevention. This might take the form of regular massage, or injury prevention techniques such as eccentric loading exercises, which have been shown to be very effective at reducing the risk and severity of symptoms of tendon injuries, especially Achilles tendon injuries. From the perspective of bone injuries, regular exercise has been show to increase bone strength, so it might be a factor to motivate those at an increased risk of bone injury (such as the elderly) to exercise a bit more, as well as consume more nutrients that have been potentially associated with an increase in bone health (such as 800iu Vitamin D and 1000mg of calcium daily), and possibly avoiding high caffeine intakes, which can reduce bone mineral density, and therefore increase the risk of developing a fracture.
The next gene to be put under our spotlight is CRP. This gene affects both the aerobic trainability and recovery aspects of our report, as well as playing a role in the DNAFit Peak Performance algorithm. Small changes within this gene cause changes in the amount of CRP we would expect each person to have, both at baseline and following exercise. CRP stands for C-Reactive Protein, which is a marker for inflammation. The greater the amount of CRP a person has, typically the more inflammation they have.
Research indicates that higher amounts of CRP are associated with lower levels of aerobic fitness (as measured by VO2max). Research typically shows that G allele carriers of the CRP SNP we are interested in will typically have higher levels of CRP both at baseline and after exercise, which could affect how much they will improve following aerobic endurance based training – typically we would expect smaller improvements in these people. The opposite is also true; A allele carriers of CRP will be more likely to see greater improvements in aerobic capacity, and better improvements from endurance training than G allele carriers.
CRP is also released after exercise, and again G allele carriers are likely to have a higher amount of CRP following exercise. This causes a greater amount of inflammation, which in turn means it can take longer for recovery to occur. Because of this, we will class people with at least one G allele as having a slower recovery speed than AA genotypes. The good news is that small changes in our diet can have a really positive effect on lowering CRP levels and improving recovery. A 2003 study looked at the effect of a supplement containing omega-3, vitamin E and polyphenols (nutrients found in fruits and vegetables) on CRP release following exercise. What the researchers found is the less CRP was released following exercise when the supplement was taken, and this helped recovery; those taking the supplement saw shorter recovery times. So, if we know you’re likely to have higher levels of CRP following exercise, we would recommend that you consume higher amount of antioxidants through fruits and vegetables, as well as fish oils, in order to improve your recovery speed.
In summary, a polymorphism within the CRP gene can affect how well you recover from exercise, as well as affecting improvements from exercise.
Continuing our focus on specific genes, we place FTO under the microscope. This gene plays a role in determining how well we deal with fats, especially saturated fats, but it is also implicated in obesity risk – as such, FTO is called the fat mass and obesity-associated gene.
We don’t necessarily know why this gene is linked to obesity and weight gain, especially with diets high in fat, although recent research appears to suggest that it could be due to differences in levels of certain hormones, particularly ghrelin, which stimulate appetite. The research on FTO, though, does show that the gene has an effect on how well we tolerate fat in our diet, especially saturated fat. Two studies conducted by a research group headed by Emily Sonestedt illustrate this really nicely. The first, from 2009 looked at the effects of the FTO gene in 4839 men and women born in Malmo, Sweden, between 1923 and 1950. The researchers asked the subjects questions about their dietary intake and leisure time physical activity, and the subjects were weighed and had their height measured - from this their Body Mass Index (BMI) was calculated. What the researchers found was interesting; the FTO gene appeared to interact with the macronutrients found in the diet to have an effect on BMI. Those people with the AA genotype of FTO were over twice as likely to be obese on a high fat diet compared to the TT genotypes. On a low fat diet, this risk had reduced to almost the same as the TT genotypes.
The second study from this research group was published in 2011, and again found that fat intake interacted with FTO genotype to have an impact on body fat percentage.
The trends showed, quite nicely, that those with the TT genotype don’t see an increase in body fat with a concurrent increase in fat intake; whilst those with the AA genotype do. In the highest quintile of fat intake, those with the AA genotype had a body fat almost one percentage point higher than those with the TT genotype. Similar results were found by another research group, headed by Corella, in 2011, but this time looking especially at saturated fat.
So what does this all mean? Essentially, those with the A allele of FTO should consume less saturated fat compared to those with the TT genotype, because they are more at risk of fat gain when intakes of saturated fat are higher. The good news is that exercise and healthy eating also help to almost completely mitigate any risks associated with FTO genotype – hopefully motivating people to exercise and follow a healthful diet more regularly.
We now turn our attention to a gene called ADRB2, which plays a role in response to exercise, VO2max trainability, and sensitivity to both fats and carbohydrates. When talking about ADRB2, we are actually interested in two single nucleotide polymorphisms (SNPs) found in the gene, given the imaginative and catchy names of Arg16Gly and Gln27Glu. This gene codes for something called the beta-2 adrenergic receptor, whose job it is to bind to adrenaline.
The small changes in this gene that we are interested in are therefore related to how sensitive our body can be to the effects of adrenaline. As such, changes in this gene can affect the heart, increasing heart rate, allowing more blood to be pumped around the body, transporting nutrients and oxygen to muscle; increasing the size of our bronchus and bronchioles (commonly known as the windpipe), allowing more oxygen to be taken in to the body; and increasing the breakdown for fat as use for a fuel during exercise. Due to these effects, different versions of ADRB2 have been associated with better response to endurance exercise, and also better improvements in VO2max.
One study that looked at this, for example, was published in 2007. The researchers compared a group of elite endurance athletes with a group of sedentary people. The elite athletes all had a VO2max of over 75ml/kg/min, whilst the sedentary people all had a VO2max of under 50ml/kg/min. After analysing the groups, it was found that those with the G allele of the Arg16Gly SNP were more likely to be in the sedentary group, whilst the A allele was over-represented in the elite athletes. Similar results have been found for the Gln27Glu SNP, with the G allele again associated with a lower VO2max.
So that’s the response to exercise, but this gene also plays a role in carbohydrate sensitivity. A paper published in 2003 in The Journal of Nutrition found that G allele carriers of the Gln27Glu polymorphism were more sensitive to carbohydrates, such that with a high carbohydrate intake, those people had a much higher obesity risk. Other research suggests that this gene can affect how much weight people lose when on an energy-restricted diet.
Overall, then, the two SNPs within ADRB2 can have an impact on how well you respond to both training and carbohydrates and fats.
SOD2 is the gene that creates Manganese Superoxide Dismutase-2 (MnSOD2), an antioxidant found in the mitochondria – small “cells within our cells” which are where our body produces energy for both movement and everyday life. The enzyme helps to convert free radicals, which can cause damage to the mitochondria, into oxygen and hydrogen peroxide. This prevents the free radicals from causing too much damage, but hydrogen peroxide in and of itself can also damage the mitochondria. Our body then has to further break down this hydrogen peroxide to water, and two other enzymes help in this process, called catalase and glutathione peroxidase.
A single nucleotide polymorphism (SNP) in the SOD2 gene can change the structure of the protein found in the MnSOD2 enzyme, which can make it more or less efficient. The more efficient this enzyme is, the better you are at reducing free radicals to hydrogen peroxide and water. Whilst this might sound good, it has a secondary effect of increasing the amount of hydrogen peroxide that will be present, which, as already mentioned, can be damaging. Because the other enzymes, catalase and glutathione peroxidase, are supported by antioxidants, low intakes of antioxidants will lead to an increase in hydrogen peroxide build up, which will damage the mitochondria. So, whilst having a more efficient MnSOD2 enzyme might sound good, if your overall antioxidant intake is low, it can actually increase risk over time.
What we know from a number of different studies is that the C allele of SOD2 is associated with a more efficient MnSOD2 enzyme – so if antioxidant intake is high, this is good, but if it is low, this is not ideal. We see this from studies such as this one by Li and colleagues, published in 2005. In this study, they looked at 567 people who developed prostate cancer, and compared them to 764 people who didn’t. They compared SOD2 genotype between the groups, and also how many antioxidants each person consumed on a regular basis. What they found was that, when antioxidant intake was low, those with the CC genotype had a much higher risk of developing prostate cancer compared to the CT & TT genotypes – about 2.5 times higher. However, if antioxidant intake was high, their risk dropped, significantly, to around half that of those with the CT & TT genotypes.
This is a really good example of how genes aren’t good or bad, just dependent on the situation; in this example, the CC genotype carries the risk if antioxidant intake is low, but is protective if antioxidant intake is high.
At DNAFit, we take a food first approach, so if you see you have a raised need for antioxidants, we think it’s a good idea to get this from fruits and vegetables, as these foods are highest in these nutrients. The most common forms of antioxidants are vitamin A (found in carrots and sweet potato), vitamin C (found in broccoli, peppers and oranges), and vitamin E (found in almonds and sunflower seeds). There are also other antioxidant compounds, such as carotenoids (found in colourful fruits and vegetables) and polyphenols (found in teas, coffee, wine and chocolate – it’s not all bad news!). All of these nutrients are important, so for those of you with a raised need, we recommend eating a wide range of fruits and vegetables per day, along with different teas, coffee, and maybe a few squares of dark chocolate with a glass of wine in the evening – depending on your fat loss goals of course.
Our attention now turns to IL-6, a gene that appears in a number of our trait reports – it can affect the power-endurance response, recovery speed, injury risk, and omega-3 requirements.
The IL-6 gene can play a role in determining how much interleukin-6 (IL-6) you might produce, either at resting or as a response to exercise. IL-6 causes inflammation, and those with the C allele of this gene are likely to have higher levels of inflammation than those with the G allele. This can affect both recovery, injury risk, and how well you respond to power training. This latter point was reported in a study published in 2010, looking at different genotypes of this gene in elite Spanish power and endurance athletes. It was found that the G allele was more common in elite power athletes compared to the endurance athletes, allowing the researchers to conclude that it plays a role in response to power training. Similar results were found in a 2013 study comparing elite power athletes with non-athletes. Once again, the G allele was significantly more common in the power athletes compared to the non-athletes.
In terms of recovery, this gene can play in role in determining how much time you need between your hardest sessions. A study published in 2008 got a group of subjects to do some bicep curls to failure, focusing on lowering the weight as slowly as possible, in order to damage the muscle. They then measured markers of muscle damage found in the blood, such as creatine kinase (CK), and found that the CC genotype of IL-6 had the highest levels of CK, and those with the GG genotype had the lowest, indicating that GG genotypes recover the quickest.
Finally, we have IL-6 and its role in general health. Because IL-6 can drive inflammation, it has been implicated in a number of diseases that are inflammatory in nature, including coronary heart disease. A paper from 2001 showed that those with the C allele of this gene had an increased risk of coronary heart disease and hypertension compared to G allele carriers. If we know this, then we can recommend higher amounts of omega-3, which has anti-inflammatory effects within the body. If we see that you have a risk allele of IL-6 or TNF, another gene with inflammatory effects, DNAFit will recommend extra amounts of omega-3 above the recommended daily allowance of 1.6g per day; in this case, up to 3g of omega-3 per day.
For the first time we focus on not one gene, but two that play a role in determining our requirements of cruciferous vegetables, which include broccoli, cabbage, cauliflower, kale, and everyone’s favorite, Brussels sprouts. These foods contain plenty of compounds that are beneficial for our health, but one that we are most interested in for these genes are glucosinolates, which have been researched for their effects on cancers.
Within the body, these glucosinolates are metabolized to something called isothiocyanates, and it is this substance which potentially has the cancer reducing effects. These genes are called GSTM1 and GSTT1, and they form enzymes that are part of the phase-II detoxification pathway – the way our body gets rids of various toxins, including medications and pesticides found in food. These genes are subject to something called an insertion/deletion polymorphism, similar to a gene we met earlier, ACE. Individuals with the inserted genotype have good function of these enzymes, and those with the deleted genotype have a reduced function, which could be problematic if cruciferous vegetable intake was low. It’s estimated that about 50% of people have the deleted form of GSTM1, and about 25% of people have the deleted form of GSTT1.
A study from 2003 looked at the impact of these genes on markers of DNA damage in 634 subjects, taken from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Blood tests were carried out to test for DNA damage, and the subjects were genotyped for a number of genes, including GSTM1 and GSTT1. When looking at the impact of diet and GSTM1 on DNA adducts (a segment of DNA bound to a cancer causing chemical), there was found to be a very strong relationship between those who ate the greatest amount of leafy vegetables - including cruciferous vegetables - and DNA adducts; those eating the most of these vegetables had the lowest amount of adducts. An interesting finding occurs when you compare those with the GSTM1 insertion genotype with those who have the GSTM1 deletion genotype; in the lowest two tertiles for green leafy vegetable intake, those with the deletion genotype have greater amounts of DNA adducts, whilst in the highest tertile, they actually have lower amounts of adducts compared to the insertion group. This effect could well be because both GSTM1 and GSTT1 enzymes metabolize Isothiocyanates, those healthful compounds found in cruciferous vegetables, and so having the deletion genotype means that a person metabolizes them slower, allowing them to have their effect for longer. This is a great example of how the environment has a big role to play in the risk associated with certain genes; the same genotype can be “good” or “bad” depending on the environment.
Based on these two genes, DNAFit can make some general recommendations. If you have the inserted (I) version of both genes, we would recommend that you consume the normal amount of cruciferous vegetables; around 1-2 servings per week as a minimum. However, if you have at least one deleted (D) version, we recommend a higher amount of cruciferous vegetable intake – a minimum of 3-4 servings per week.
We look at a gene that plays a role in both the power/endurance and aerobic trainability aspect of our report. This gene is VEGF, and it creates Vascular Endothelial Growth Factor, which plays a role in the creation of new blood vessels. This is a useful adaptation to aerobic training, because more blood vessels around the muscle mean better, more efficient transport of oxygen, as well as fuel sources such as carbohydrates and fats, to the muscle; this in turn improves how well a person can use oxygen and exercise aerobically. When we exercise, our muscle cells quite often don’t get as much oxygen as they need. This causes the VEGF gene to be “turned on”, with transcription upregulated and more VEGF formed – leading to this increased growth of new blood vessels.
Differences in the VEGF gene, the so-called Single Nucleotide Polymorphisms (SNPs) that we are always interested in at DNAFit, could be one of the aspects that cause differences between individuals in terms of VO2max improvements to exercise. A paper published in 2006 tested this in a group of sedentary subjects, putting them through a standardised 24-week aerobic training programme, where they training three times each week for up to 40 minutes at a time. Before and after this training programme, they did a VO2max test, and also had their blood tested for levels of VEGF. What was found by the researchers was that for the SNP within the VEGF gene that we are interested in (rs2010963), the G allele was associated with lower levels of the VEGF protein (indicating lower expression of the VEGF gene), and the C allele with higher levels of the protein (and therefore greater expression of the gene). This in turn had an effect on the improvements in VO2max seen with exercise, with the C allele being associated with greater improvements. Similar results were published by a group of Russian researchers in 2008 this time on a study conducted in elite athletes. Those with the CC and CG genotype had higher VO2max values than those with the GG genotype, again indicating that the C allele is associated with greater improvements as a response to aerobic training.
In summary, then, we can see that the C allele of VEGF is associated with greater improvements in aerobic capacity following training. It also has a role to play in response to power and endurance exercise, with C allele carriers showing a better response to endurance training than GG genotypes.
We now focus on PPARA, a gene that affects how well we can respond to different types of training, and as a result appears in our power-endurance algorithm. PPARA creates peroxisome proliferator-activated receptor alpha, a protein which activates other genes, as well as being a regulator of fatty acid oxidation during exercise. The gene is activated when our cells aren’t getting enough energy, such as when we fast, or when we take part in exercise that uses up our energy stores, such as endurance exercise.
One study that has looked at differences within this gene, and its effect on endurance performance, was published in the European Journal of Applied Physiology in 2006. In this study, the researchers looked at the PPARA gene in 786 Russian athletes across a wide range of sports, both power-based and endurance-based. It was found that the G allele was much more common in endurance athletes than power athletes; about 80% of endurance athletes had the GG genotype, compared to only 50% of the power athletes. These same researchers then took some muscle fibres from the quadriceps of 40 young men. Those that had the GG genotype of PPARA had significantly higher percentages of slow-twitch muscle fibres, the type that are better at endurance based activities, compared to CC genotypes. The same is true for Lithuanian athletes, with the G allele much more common in those taking part in endurance sports.
So, if the G allele is associated with increased endurance performance, might the C allele be associated with increased power performance? Well, the study from the previous paragraph would seem to suggest so; the C allele was much more prevalent in power athletes compared to endurance athletes, and CC genotypes had greater amounts of fast twitch muscle fibre, the type that is useful to power athletes, compared to GG genotypes. A 2012 study looked at the impact of this gene on strength levels of middle-school aged children, finding that the C allele was associated with greater handgrip strength compared to the G allele.
In conclusion, it can be seen that variation in PPARA can affect how well each individual responds to both power and endurance based training.
If you've ever heard that a glass of red wine per day is good for your heart, this is truer for some people than others. Plenty of research has shown that moderate amounts of alcohol consumption can protect against risks of heart disease. For example, a study published in 1997 found that alcohol intake was associated with a protective effect against coronary heart disease in a sample of almost 130,000 people - this effect was present for both beer and wine. A second study, again from 1997, found that in both men and women, rates of cardiovascular disease were 30-40% lower in those consuming at least one drink per day compared to abstainers.
The positive effects of alcohol on your heart might be caused by alcohol affecting people’s cholesterol - specifically, alcohol might increase HDL cholesterol (often called “good” cholesterol). If alcohol is present in the blood for a long period of time, it has longer to interact with the cholesterol, and so may have a greater protective effect. The gene that interests us here is called ADH1C, which creates an enzyme that enables us to metabolise alcohol. Differences in this gene can split individuals into two camps; those with the AA genotype, called fast metabolisers of alcohol, and those with a G allele (so AG and GG genotypes), called slow metabolisers of alcohol. Based on this, we would expect that moderate amounts of alcohol consumption would have a greater positive effect on a person’s cardiovascular risk if they were a slow metaboliser of alcohol – i.e. if they have a G allele of ADH1C. And this is more or less what the studies find. As an example, a study published in 2008 examined 3700 people over an eight-year period. The participants were asked how much alcohol they consumed on a regular basis, and also had blood tests to collect various measures of cardiovascular health, including HDL cholesterol. What they found was that, in those people classed as slow metabolisers, and who reported moderate alcohol consumption, there was a 64% reduction in cardiovascular disease risk. Similar results were reported in research looking at the Framingham Offspring Study, a large study based in the US with just over 5,000 subjects, which showed, again, a lower cardiovascular disease risk with moderate alcohol consumption in slow metabolisers compared to fast metabolisers. Similarly, a 2005 study reported a 78% reduction in cardiovascular disease risk in slow metabolisers consuming moderate amounts of alcohol compared to those who were fast metabolisers.
All of this goes to show that for slow metabolisers of alcohol, those with the G allele of ADH1C, appear to find that moderate alcohol consumption has a greater protective effect against heart disease than for fast metabolisers (AA genotypes). This doesn’t mean that alcohol is bad for fast metabolisers, just perhaps not as good as it is for slow metabolisers. And with slow metabolisers, the key word when it comes to alcohol is moderate; this is not an excuse to drink excessive amounts!
AGT is a gene that appears in both our fitness and diet reports. This gene plays a role in how well we respond to power-based training, and so appears in our power-endurance profile, and also plays a role in blood pressure control, and hence appears in our salt sensitivity section. AGT is similar to ACE, a gene we looked at earlier in this series, in that it creates a protein that can cause our blood pressure to go up or down – the protein in this case being called angiotensinogen.
One of the studies showing the effect of this gene on training response was published in 2009. Researchers from Madrid University got a group of elite Spanish power athletes, endurance athletes, and non-athletes, and looked for differences in AGT genotype between the groups. The CC genotype of AGT was significantly higher in the power group of athletes than either the endurance or non-athlete groups. If a subject had the CC genotype, they were about 1.6 times more likely to be in the power group than any of the others. The mechanism behind this is that those with the C allele of this gene have higher levels of angiotensinogen in the blood. This in turn leads to higher levels of angiotensin II, similar to the D allele of ACE. As angiotensin II is a growth factor for muscles, higher levels of it would likely lead to greater muscle growth following strength training – which is why it’s more common in elite power athletes, and in turn would lead to an increased response to strength training in those looking to gain muscle.
Whilst the AGT C allele is associated with an increased response to power-based training, it’s also linked to an increased sensitivity to salt. A study from 1997 showed that the C allele was associated with an increased risk overall of hypertension, whilst later studies showed that a reduction of sodium, the main ingredient in salt, reduced blood pressure to a greater extent in C allele carriers than T allele carriers, showing that sodium reduction can be very important to C allele carriers.
The next gene to be subject to our attention is COL1A1, a gene that can play a role in determining your injury risk. COL1A1 encodes for Type-I collagen, which is one of the main constituents of collagen, a structural component found in ligaments and tendons.
One of the first studies to examine the COL1A1 gene took part in Sweden, in the orthopaedic department at Uppsala University Hospital. Here, over the course of five years, 358 patients suffering from either an anterior cruciate ligament (ACL – a ligament in your knee) injury or a shoulder injury (including one unlucky person with both) were recruited and genotyped for COL1A1. The distribution of the different COL1A1 genotypes was then compared to a group of people who hadn’t suffered an ACL injury or shoulder dislocation. Within the injury group, a specific genotype was incredibly uncommon, occurring in just 0.5% of people with either an ACL injury or shoulder dislocation, compared to 4% of injury free subjects. These individuals had the TT genotype, indicating that this could potentially be protective against injury. These results have been replicated in a number of other studies, most often from a group of researchers based at the University of Cape Town under Professor Malcolm Collins. When this group examined COL1A1 genotypes between ACL injury patients and non-patients, they found no-one in the injury group had the TT genotype, whilst 5% of those in the non-injury group did.
From this, we can come to the conclusion that having the TT genotype is protective against soft tissue injuries, as that genotype is very uncommon in the groups of injured patients studied. The reason for this is that the T allele appears to increase the expression of COL1A1, allowing more type-1 collagen to form, potentially resulting in stronger ligaments and tendons. We can use this information to tell us that the TT genotype is associated with a reduced chance of injury, and the G allele with an increased risk of injury.
If you’ve got an increased injury risk, it might seem like bad news, but really it isn’t. It’s just news that we can use to improve our training programme design, and hence your performance. If you have a high injury risk, this means that you should be proactive in your approach to injury prevention, by increasing the strength of the supporting muscles, as well as range of motion if required.
For example, runners have an increased risk of suffering from injuries to the Achilles tendon; to reduce this risk, they can undergo an eccentric training programme which has been shown to be very effective at reducing the changes of Achilles’ injuries. They could also work on the strength in their feet and calves, as well as ankle flexibility. Finally, they could ensure that their trainers are providing the required support, that the frequency of their running sessions is appropriate, and the surfaces they are running on are not increasing their injury risk. Overall, this injury risk information is not designed to scare you, but to give you the power to reduce your injury risk.
Our attention is on another gene that is found as part of our Peak Performance algorithm, which has been shown to enhance response to a resistance training programme. The gene we are focusing on this week is BDKRB2, which encodes for the bradykinin B2 receptor, which comprises one of the pathways through which bradykinin can exert its influence. Bradykinin itself is a protein that causes dilation (widening) of blood vessels, making it easier for blood to move to certain areas of the body. The effects of this gene are closely linked to the of ACE, which is a gene we met earlier in this series. Angiotensin-Converting Enzyme, which is produced by the ACE gene, also breaks down bradykinin, such that ACE II genotypes (who have lower levels of ACE) should theoretically have higher levels of bradykinin.
When we look at BDKRB2, what we are interested in is whether a person has a specific sequence of DNA called a base-pair repeat; those that have this sequence are said to have the +9 allele, and those without it are said to have the -9 allele. As you might remember, typically at DNAFit we report alleles as A, T, C or G - the individual base nucleotides that make up DNA - and so when giving information on this gene we report the +9 variant as the C allele, and the -9 variant as the T allele. The T allele (-9 variant) is associated with higher amounts of BDKRB2 being produced – and this is thought to increase response to endurance exercise.
This has been looked at in a number of studies, including one published in 2003 in the Journal of Applied Physiology. In this paper, the researchers got a group of males and females, and got them to do a series of exercises on a stationary bike to test for muscular efficiency – how much energy they used during exercise. The better the efficiency, the better that person is likely to be at prolonged exercise, as they are likely to use less energy for a given amount of work, and hence can exercise for longer. Those subjects with the TT genotype were found to have greater efficiency than the CC genotype, suggesting they might respond better to endurance exercise. Within the same paper, the researchers also looked at a group of 91 elite British athletes, and found that the T allele was much more common in endurance athletes (5000m runners+) than it was in sprinters and middle distance runners – again suggesting that the T allele is associated with a better response to endurance exercise. Similar results have been reported in other studies, including one conducted in elite triathletes; again, the T allele was more prevalent in the endurance athletes than a control group.
All of this suggests that those with the T allele should see greater improvements following endurance exercise than those with the CC genotype, and so might be well placed to focus on endurance activities slightly more within their training.
PPARG appears in both our carbohydrate and fat sensitivity panels within our diet report. This gene creates a protein known as peroxisome proliferator-activated receptor gamma, which plays a role in the formation of fat cells, as well as the use of fats and carbohydrates as a source of energy.
The single nucleotide polymorphism we are most interested in is known as Pro12Ala, and results from the amino acid proline (Pro) being substitute for the amino acid alanine (Ala). The Ala form of this gene, denoted by a G allele, is associated with a reduced expression of certain genes, which is thought to reduce the risk of weight gain – as such, C allele carriers have an increased risk of weight gain, especially when dietary carbohydrates or saturated fat is high. The C allele is also associated with an increased risk of developing insulin resistance, which can lead to type-II diabetes, and also contribute to the development of metabolic syndrome.
A study published in the journal Human Molecular Genetics in 2003 examined the relationship between the different PPARG genotypes and risk of obesity. After collecting data from 2141 women, the researchers calculated an average daily intake of fat for each person, and compared it to their BMI. They found that the Pro12Ala SNP had an effect on the risk of obesity at different intakes of fat. For CC (Pro-Pro) genotypes, those in the highest 20% of fat intake had a higher risk of obesity than those in the lower intake groups, and in fact they were over three times more likely to be obese compared to those in the lowest 20%W of fat intake. However, in GG (Ala-Ala) genotypes, this relationship didn’t exist – showing quite nicely that those with the C allele are perhaps more sensitive to increases in BMI with higher intakes of both fats and carbohydrates, and so might be well placed with a more balanced diet, such as the Mediterranean Diet, with its focus on whole grains, lean protein, and moderate amounts of dairy products and olive oils.
The above study, and others like it, are a great example of why a one-size-fits-all approach to dieting is not ideal – because of differences in our genes, but also our environment, what works for one person might not work for another. That’s why knowing and understanding what versions of key genes, such as PPARG, that you possess can be really useful in enhancing weight loss, or reducing weight gain.
We look in depth at NRF-2, a gene that appears in our power-endurance panel. This gene creates nuclear respiratory factor 2, which plays a role in allowing some of the improvements that happen following endurance training, including increases in the number of mitochondria we have, a process called mitochondrial biogenesis. There are a number of single nucleotide polymorphisms (SNPs) within this gene, but the one we are most interested in is rs7181866, as this one has the most evidence supporting its inclusion in our panel.
One of the first studies to look at this SNP was published in the International Journal of Sports Medicine in 2007. In this bit of research, a group of Chinese men were put through an 18-week endurance training programme, and monitored for improvements in VO2max, a measure of aerobic capacity. The G allele of the SNP of interest was found to be associated with a much higher improvement in VO2max following training than those with the A allele. These results were replicated in a group of Israeli athletes in 2009. The GG genotype was discovered to be very rare – none of the 155 athletes or 240 controls studied had it. However, the AG genotype, and hence the G allele, was significantly more likely in endurance athletes compared to both sprinters and controls, and the higher the standard of the endurance athlete, the more likely they were to have a G allele. Similar results were found in a 2012 study in Polish rowers with the G allele being more prevalent in the rowers, who are classed an endurance athletes, when compared to controls
Results from studies like the ones detailed above are why NRF2 forms part of the DNAFit Peak Performance Algorithm; typically, we would expect those with a G allele to see a greater improvement in fitness when following endurance exercise. This information, and all that is included in the Peak Performance algorithm, can be useful in helping you to discover which training works best for you, allowing you to see greater improvements in fitness.
This edition’s gene is TNF, which creates tumour necrosis factor. TNF is a pro-inflammatory cytokine - higher levels of TNF are associated with higher levels of inflammation, which can have an impact on various health risks, as well as our ability to recover from exercise. Higher levels of TNF following exercise are associated with higher levels of C-Reactive Protein (CRP); this drives inflammation, requiring longer recovery times between hard training sessions.
The SNP within TNF that we are most interested in is called G-308A (rs1800629). Here, a substitution of the guanine (G) base nucleotide for adenine (A) leads to higher levels of TNF. We would therefore expect that AA genotypes would need for longer recovery times compared to G allele carriers. A study published in 2006 as part of the HERITAGE study confirmed this. In almost 700 subjects, the researchers measured CRP before and after a 20-week endurance training programme. At baseline, AA genotypes were much more likely to have higher levels of CRP compared to G allele carriers. Following the 20-week training programme, this association was further confirmed; CRP levels increased to a greater extent in AA genotypes than G allele carriers – again indicating that A allele carriers might need longer recovery periods between intense exercise sessions.
The same is true when it comes to general health. A 2016 study found that the A allele was associated with an increased risk of frailty in the elderly. Similarly, a 2014 study found that there was an increased risk of rheumatoid arthritis, a disease with high levels of inflammation, in A allele carriers.
What can we do about this? Well, omega-3 fatty acids have been found to be effective in reducing inflammation. These fats are polyunsaturated fatty acids, most commonly found in oily fish (but also in some vegetarian friendly sources such as flax seed). We can’t make omega-3 within our body, which means we depend on our diet to provide them. A meta-analysis published in 2014 found that fish oils had a lowering effect on TNF levels. Similarly, a 2006 systematic review published found that an increased consumption of fish oil reduced the risk of all-cause mortality, cardiac death, and possibly stroke death. The recommended daily allowance (RDA) for omega-3 is 1.6g per day; we might consider that those a risk allele of TNF consume up to twice this amount (3g) per day. This is especially important, as omega-3 fatty acids appear to be more effective in individuals with a risk allele of TNF. For example, a 2002 study found that fish oil was the most effective in those with the highest levels of TNF pre-supplementation. It seems logical to suggest that, if we know someone is more likely to have higher levels of these inflammatory markers due to their genes, they might have an increased need for omega-3 fatty acids, especially fish oils
We’ve seen that TNF can affect our speed of recovery and also our general health, and that omega-3s, most commonly found it fish, should help to reduce inflammation. 150g of oily fish such as salmon or mackerel will contain about 3g of omega-3 – so you can have oily fish every other day, or maybe an omega-3 tablet if you don’t eat fish.
Now we turn our attention to FABP2, a gene that appears in both the carbohydrate and saturated fat parts of our reports. This gene creates a protein called Fatty Acid Binding Protein-2, which is found in our small intestines. FABP2 binds to the various different fatty acids, and allows them to be absorbed into the body.
The single nucleotide polymorphism (SNP) that we are interested in occurs when an alanine nucleotide is swapped for a threonine nucleotide; this substitution causes the protein to become more efficient. So efficient, in fact, that it doubles the speed at which we absorb these fats, leading to an increase of fat in the bloodstream.
What effect does this have in the real world? One study, published in 2007 in the American Journal of Clinical Nutrition gives us some idea. The researchers got 122 elderly adults, and put them through a number of different tests to see how they tolerated different types of foods. Those with at least one A allele of FABP2 were less likely to have normal blood glucose levels, both after fasting and after having a big meal. This indicates that they were at risk of developing insulin resistance, which can eventually become type-II diabetes. If we know that A allele carriers are more likely to develop type-II diabetes, then we can give them dietary advice which might help to reduce their risk, such as consuming a diet lower in simple and refined carbohydrates.
We’ve looked at the effects of FABP2 on our carbohydrate sensitivity, but how about saturated fats? A meta-analysis published in 2010 gives us an insight into this. Meta-analyses are useful tools for researchers and medical professionals, as they analyse the data of existing research in a particular area, and summarise it to give us a better idea of the current evidence in that field. The results from this meta-analysis looked at 30 different studies, with over 14,000 subjects. It found that A-allele carriers of FABP2 were significantly more likely to have higher concentrations of total- and LDL-cholesterol (LDL cholesterol is commonly known as “bad” cholesterol), and lower levels of HDL-cholesterol (“good” cholesterol) – showing quite nicely that this gene influences how much fat we should have in our diet.
We use FABP2 alongside a number of other genes to give each person an idea of their individual response to both carbohydrates and fats, information that we can then use to determine the optimal diet type for weight management.
Again, we look at two genes that form part of our antioxidant needs section of the DNAFit Diet report, called CAT and GPX1. The gene that carries the most weight in this section is SOD2, which we have looked at previously in this series. If you can’t remember that far back, SOD2 is an antioxidant enzyme, and small changes in the SOD2 gene can lead to that enzyme working better or worse, which can increase how much of the antioxidant nutrients you require. CAT and GPX1 play a supportive role here.
The CAT gene produces an enzyme called catalase, which helps break down hydrogen peroxide, a substance that is very toxic to our cells, into water and oxygen. If we have a build up of hydrogen peroxide within our cells, this can cause a lot of damage, which could theoretically increase our risks of various diseases and illness. Catalase is a very strong enzyme, with one molecule of catalase able to breakdown millions of hydrogen peroxide molecules every second. GPX1 creates glutathione peroxidase 1, an enzyme that also helps to breakdown hydrogen peroxide, and therefore protect our cells from damage.
Given the important functions of these enzymes, it should be obvious that keeping them working well and at adequate levels in the body is important. However, single nucleotide polymorphisms (SNPs) in these genes can lead to the enzymes working less well in some people compared to others. A study published in 2006 looked at this in some detail. 231 young men and women had blood samples taken and analysed for how active both the CAT and GPX1 enzymes were, and then compared against their genotypes for these genes. In both the male and female subjects, GPX1 activity was lowest in the TT genotypes, and highest in the C allele carriers. The same was true for catalase; TT genotype had the lowest activity of this enzyme, then CT genotypes, and then finally CC genotypes. Other studies have reported similar results for both catalase and GPX1.
So, if we know that a person has a version of a gene that predisposes them to have lower levels of enzyme activity, what can we do about it? Firstly, it would be a good idea to consume higher than normal amounts of antioxidant nutrients, such as the vitamins A, C, and E. Whilst the recommended daily allowances might be sufficient for certain people, those with the lower activity genotypes of these genes might be well suited to having more of those nutrients. This can be as simple as focusing on brightly coloured vegetables, such as sweet potatoes and peppers, and almonds and seeds for vitamin E. When it comes to GPX1, this enzyme has been found to respond well to higher levels of selenium, and so in those with the CT or TT genotypes, a selenium intake of just above the RDA (we recommend 90mcg for CT and 105mcg for TT genotypes; the RDA is 75mcg per day). Seafood and Brazil nuts are the foods highest in selenium; roughly 2-3 Brazil nuts per day would give you all the selenium you need.
To summarise, different versions of two genes, CAT and GPX1 can predispose an individual to require higher than normal amounts of antioxidants and selenium.
We are now going to focus on PPARGC1A, or as we call it at DNAFit, “the one with the long name”. This gene encodes for a protein called peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), which causes some of the positive changes that occur in our body following exercise. One of the ways that exercise can lead to improvements is through something called mitochondrial biogenesis, which is the production of new mitochondria within the muscle itself.
Mitochondria are often called “cells within a cell”, and, as you might remember from school, they are where energy is produced - if we have more mitochondria, then we can better produce this energy, which in turn allows us to exercise for longer, making us fitter. When our muscle cells aren’t getting enough energy to allow us to continue to exercise, then PPARGC1A becomes switched on, allowing for an increase in PGC-1a production. PGC-1a then interacts with other genes such as PPARA and NRF (genes that we also test for at DNAFit), all of which allow these positive adaptations to exercise to occur. The PPARGC1A gene is important, because different versions of this gene allow more or less of this protein to be produced, which can affect how well we respond to certain types of training. Typically, we would expect GG genotypes to produce more of this protein, and AA genotypes to produce the least.
One paper that has looked at differences in PPARGC1A genotype and its effect on performance was published in 2005 in the Journal of Applied Physiology. In this study a group of World-Class Spanish male endurance athletes (runners and cyclists) were compared to a group of unfit UK males, to see if there was any difference in PPARGC1A genotypes between them. The researchers found that the A allele of PPARGC1A was less common in the Spanish athletes, and in turn much more common in the group of British males. As a second part of this study, the UK subjects underwent a VO2max test, which measures how good a person is at using oxygen during exercise - typically the more aerobically fit a person is, the higher their VO2max. Following this test, the researchers ranked the subjects into two groups - those classed as “fit”, and those classed as “unfit”. Within this second part of the study, it was found that the A allele of PPARGC1A was less common in the “fit” group compared to the “unfit” group. Overall, the A allele of PPARGC1A was found in just under 30% of world-class endurance athletes in this sample, compared to just under 35% of “fit” controls, and 40% of “unfit” controls. A number of other researcher papers has confirmed the role that this gene plays in response to endurance exercise.
So what does this all mean for you? Well, at DNAFit we look at 15 different genes that affect how well you respond to certain types of training as part of our Peak Performance algorithm, and, as you might have guessed, one of those genes is PPARGC1A.
The next gene to get put under the spotlight is TRHR. This gene encodes for the thyrotropin-releasing hormone receptor, which is a receptor for a hormone called thyrotropic-releasing hormone (TRH), which is released from the hypothalamus. When TRH binds to TRHR, it causes a number of different cellular signals to occur, which in turn stimulate the thyroid gland to produce thyroxin, which in turn plays a role in the growth and development of skeletal muscle. Small changes in the TRHR gene mean that the hormone receptor is not quite as good at binding with TRH, which in turn can reduce or limit the amount of muscle that can be produced following training.
All of this sounds quite complex, which can often be the reality of looking at the effects of genes on certain traits (you should try working in this field!). However, what it means in simple terms is that people with a certain genotype of TRHR will find it easier to gain muscle mass with weight training, and will likely do so to a greater extent, than people with a different TRHR genotype. A genome wide association study published in 2009 showed this quite nicely. By grouping together the findings of three different studies, involving almost 6,500 Caucasian and Chinese subjects, researchers found that those with the GG genotype had, on average, 2.7kgs more lean body mass that subjects with the TT or GT genotypes. This leads us to conclude that those with the G allele are much more responsive to power-based training, because they have a greater ability to build muscle.
In conclusion, the TRHR gene can have an impact on how well you respond to strength training in terms of improvements in lean body mass. As such, TRHR is included in the DNAFit Peak Performance Algorithm, with the G allele carrying a positive weighting with regards to a power bias.
We are now going to be investigating ADRB3, a gene which appears in our fat sensitivity panel. This gene encodes for beta-3-adrenergic receptors, which are located mainly is fat tissue. They play a role in breaking down fat for use as energy, and a small change in this gene, known as a single nucleotide polymorphism (SNP), is thought to determine how well we can tolerate saturated fats.
Those with the C allele of this SNP are not quite as good at breaking down fat for use as energy, and so often have higher body fat levels, as well as a greater body mass index (BMI). A study from 1995 showed this quite nicely. A group of Finnish subjects were studied, and those with the C allele tended to have, on average, a higher hip to waist ratio, a risk factor for cardiovascular disease. They also were more likely to have insulin resistance, a precursor to the development of type-II diabetes. Similar results were found in a 2012 study, this time looking at Russian subjects; again, those with a C allele of ADRB3 showed a significantly higher body fat percentage, as well as markers of insulin resistance. Not only that, but this gene has been found to play a role in how well people lose weight as response to a diet and exercise programme. In a study in obese subjects published in , those with the C allele lost less fat than those with the TT genotype.
Based on the results of these studies, and others like it, we can predict that those with the C allele of ADRB3 should consume less saturated fat as part of their diet, as they are uniquely sensitive to the negative effects of this type of fat, including fat gain. That’s why this gene appears in our fat sensitivity panel; those with the TT genotype will likely be reported as less sensitive to saturated fat than those with the C allele.
The next gene we are taking a closer look at is IL6R. This gene is closely related to IL6, which we discussed a few months ago, as it encodes for Interleukin-6 receptor, which is what IL6 binds to – influencing the action of IL6 within the body. There are two different alleles associated with this single nucleotide polymorphism (SNP); the C allele and the A allele.
Typically, those with at least one C allele tend to have higher levels of IL6R. This was shown in a 2004 study, whereby in a group of 70 subjects, those that were C allele carriers had significantly higher levels of IL6R. This is important because higher levels of IL6R within the blood tend to mean higher levels of IL6 too. For example, a 2007 study found that those with the CC genotype had almost 1.5 times higher levels of IL6 compared to AA genotypes, whilst AC genotypes had about 1.1 times higher levels.
So why might this be important to know? Well, if you can cast your mind back to the article on IL6, you might remember that IL6 is something that causes us to become fatigued. We know this from a number of studies conducted by Robson-Ansley and colleagues. In one of these studies, published in 2007 it was seen that heavy training loads in triathletes caused an increase in IL6 for an extended period of time, which might in turn reduce immune function. An earlier study by the same lead author published in 2004 found that giving runners IL6 caused them to run slower and feel more fatigued.
If we know that elevated IL6 might be bad news, and we know that the C allele of IL6R might contribute to this, we can use this information to enhance our recovery. In the DNAFit Fitness Report, we look at how quickly an individual can recover in between training sessions – and one of the genes we look at here is IL6R. If we can see that you’re likely to have higher levels of IL6 following exercise, we can recommend longer recovery times between your hardest training sessions, in order to prevent you from overtraining and potentially becoming injured. We can also give you recommendations on what nutrients to consume, including omega-3, which can potentially lower levels of IL6 within the blood.
Overall, we can see that different genotypes of IL6R, summarised in the table below, can have different responses to the same training session, especially in regards to IL6, which might increase the time needed to recover.
It is now known that there are two genes, called HLA DQ2 and HLA DQ8, which are found in about 99% of people with coeliac disease. However, these genes are also present in about 35% of people with coeliac disease. So whilst the majority of people with coeliac disease have the HLA DQ2/DQ8 gene variants, the majority of people with these genes don’t have coeliac disease. This is because coeliac disease only affects about 1% of people. So, if we have 100 people, about 35 of these people will have the HLA DQ2 or DQ8 genes, but only one of them will have coeliac disease.
Coeliac disease is an autoimmune condition that affects the small intestine. If you have coeliac disease, and you consume foods that contain gluten, you will likely suffer from symptoms include diarrhoea, abdominal pain, weight loss and malabsorption. This is because the presence of gluten causes a reaction in the microvilli, which are finger-like structures found in the small intestine. Their purpose is to increase the surface area of the intestines, allowing for greater absorption of vitamins and minerals. However, in people with coeliac disease who consume gluten, these microvilli become blunted and start to disappear – a process known as villous atrophy. This makes it much harder for the body to absorb nutrients, which in turn can causes weight loss and vitamin and mineral deficiencies.
The DNAFit test, then, can’t tell you whether you do or don’t have coeliac disease. The only way to know for sure if you have coeliac disease is through a small bowel biopsy, which would be done by a doctor. Instead, DNAFit can tell you your likelihood of developing coeliac disease. As I mentioned earlier, everyone’s risk of developing coeliac disease is 1/100 – and this is true until we test your genes. If we see that you haven’t got the HLA DQ2/DQ8 genes, then your risk of developing coeliac disease is very low; about 1 in 2000. If you have got the HLA DQ2/DQ8 genes, then your risk is elevated to 1 in 35. Still pretty good odds in your favour that you won’t have coeliac disease, but worth being aware.
So, how can you use this information? It’s worth reiterating that the DNAFit test can’t tell you whether you have or haven’t got coeliac disease, or whether you can or can’t get it. It can just tell you the likelihood of developing it. Even if you have a low genetic risk of 1 in 2000, that still means that you can develop coeliac disease. Conversely, having a higher risk of developing coeliac disease does not mean that you will. It’s worth pointing out that the only known management for coeliac disease is a gluten free diet. However, if you have the HLA DQ2 or HLA DQ8 genes, there is no reason for you to start eating this way. Instead, you should monitor how you respond to gluten containing foods. If you start to develop diarrhoea or abdominal cramps, or feel run down or anaemic, and have a high risk of coeliac disease as per the DNAFit test, it might be worth speaking with your doctor in order to have a proper medical examination.
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