Research Review: Genes vs workout program

By Helen Kollias


Genetic destiny. It’s the new version of the “devil made me do it.” But how much evidence supports this theory? And if you have a given gene, should you give up hope and succumb to your eventual fate?

It’s my genetics! That’s why I’m overweight, obsessive compulsive and/or in jail!

Genetic destiny. It’s the new version of the “devil made me do it.” But how much evidence supports this theory? And if you have a given gene, should you give up hope and succumb to your eventual fate?

Since the completion of the Human Genome project in 2003, scientists have been trying to figure out what gene does what — and what version or versions contribute to disease. BRCA1 and BRCA2 genes are probably the most well known for their association with breast and ovarian cancer.

Before I go on, it’s important to remember that it’s the mutations (changes in the genetic code) of genes, not the genes themselves that can contribute to disease.

What does that mean? Say your roof caves in and crushes your car sitting in your garage. Does that mean that roofs cause car damage? No. It means roofs with major structural problems may malfunction and may cause car damage. So if you have a normally functioning gene then everything is great, but if you have a malfunctioning (mutated) gene then things can go bad. But this doesn’t mean that 100% of the time the “roof will fall in.”

So, mutant genes can increase the likelihood of abnormal function and disease. Notice I say “likelihood”, not “inevitability”. More on that later.

Back to our example: Specific mutations in BRCA1 and BRACA2 genes do increase the likelihood of breast cancer in women by 3 to 7 times, but most women who are diagnosed with breast cancer do not actually have a mutation in the gene.[1]  Well, what does that mean? Women with BRACA1 and BRACA2 mutations should have more frequent and thorough exams, but this doesn’t mean that if you don’t have the mutations that you’re home free.

Okay, you may be thinking, but what does this have to do with me fitting into my jeans or losing my beer belly? A couple of years ago, researchers discovered that a gene on the 16th chromosome was linked to diabetes.  If that gene was mutated at a specific spot it increased the likelihood of having more fat.[2] Researchers named the gene “fat mass and obesity” (FTO) associated gene, which is unfortunate because it’s not the function of the gene, but rather what happens when it doesn’t work — kinda like naming your car “car won’t start” when it doesn’t start on a given day.

In this 2007 study, if both FTO genes were the mutated version (homozygous) then on average you would weigh at least 3 kg (6.6 lb) more than someone with “normal” FTO genes and you would have a slight increase (1.67 fold) in becoming obese. Why this happens hasn’t been figured out yet but it seems to involve energy and adipose tissue regulation that occurs at the brain (specifically the hypothalamus.)

Golden gene in DNA

Research question

So is that it? If someone has abnormal FTO genes then they’re doomed to have more fat and there’s nothing can be done? Actually no — there is something that can be done and that’s what the study I’m reviewing this week discusses.

Rampersaud E, et al. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med. 2008 Sep 8;168(16):1791-7.


This study has an interesting group of participants: 704 Older Order Amish adults (OOA). What makes this group unique is that they don’t have modern conveniences (no cars, no electricity, etc.) That means that they are much more physically active than the average person. Farming, carpentry and even blacksmithing is much more physically demanding without modern equipment. Another thing about the group is they are very similar (homogenous): they have both similar lifestyles (diet and activity) and similar genetic backgrounds, since their ancestors were from the same region in Europe.

Everybody had blood taken to be tested for different versions of the FTO gene. BMI, body composition (using dual x-ray absorptiometry, aka DEXA) and waist circumference were also measured. Researchers measured physical activity by having each participant wear an accelerometer for 7 days straight (24 hours/day). An accelerometer measures how often and how fast people move.

Average age for the group was 43.6 years old. 53% of participants were men and 47% were women. Average BMI for the men was 25.7 and 27.8 for the women. 10.1% of the men and 30.5% of the women were obese. For reference: Normal BMI =18.5-25, Overweight BMI = 25-30, Obese BMI>30.

The question: Is there a connection between fat (obesity), mutations in the FTO gene and physical activity?


Several mutations of the FTO gene correlated to increases in BMI (specifically rs1861868, rs9939609 and rs1477196.) Looking just at people who had a specific FTO gene mutation (rs1861868) the researchers found some interesting things. There was a correlation between BMI and people with this specific mutation, but only if they had low activity levels. If they were very active then there was no correlation. The difference between low and high activity levels were 860 kcal/day for women and 980 kcal/day for men. Same results for obesity: the gene mutation was correlated to obesity only at low activity levels.

Looking at another gene mutation (rs1477196), same thing: obesity and this gene mutation were also only correlated at low activity levels.

So obesity and BMI can be correlated to specific genetic FTO mutation, but in two of the three cases (mutations) physical activity levels can overcome this correlation. Meaning, if you were inactive and had a mutation in your FTO gene then you are giving yourself the best chance of being obese. By changing your FTO gene – a little difficult – or increasing your activity level you can decrease your chance of becoming obese.


So if you have one the “fat” versions of the FTO gene, but are on the higher end of physical activity then guess what – chances are you’re not obese. While the FTP gene mutation increases your chance of becoming fat if you are relatively sedentary it doesn’t mean you will get fat. All you have to do is be physically active.

You may be asking yourself: Isn’t physical activity good for everybody? Yes. So why bother with the genetic testing? It comes down to how much physical activity you need — if you have one version of the gene you could be less active and maintain normal body weight, but if you have the other version you will have to increase your activity to do the same.

The debate of nature versus nurture has been around for ages and the reality is that they are intertwined. Does nature (genetics) affect who you are? Of course. Does nurture (environment) affect who you are? Of course. But both affect each other and who you are. In this case nature may increase your likelihood of having extra fat, but changing your environment by being physically active trumps nature.



Click here to view the information sources referenced in this article.

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