May 4, 2008 - Health + Traits

MC4R Gene Associated with Body Mass

feetscale.jpgThe Atkins diet, the South Beach diet, the Grapefruit diet, the Cabbage Soup diet — we know all these fad diets have their limits, because ultimately, the only way to lose weight is to eat fewer calories and burn more.

But have you ever thought about what controls your appetite? What if your body didn’t tell you to stop eating when you’d consumed enough calories?

You’d gain weight, that’s what. It’s long been known that mutations in a gene called MC4R cause mice to become bigger and fatter than their regular counterparts.

It’s thought that eating a lot causes the body to turn on MC4R, which in turn tells the mice to stop eating by making them feel full. There are also rare variations that disrupt the human MC4R protein and cause children to eat too much, leading to severe childhood obesity.

Interesting, you say, but does this apply to the general population too? Research published online Sunday in the journal Nature Genetics suggests that the answer is yes.

A large study of over 77,000 Europeans by Loos et al. found a SNP near the MC4R gene, rs17782313, that was strongly associated with body mass index (BMI), a measure of obesity. (To calculate your own BMI, go to: They found that each copy of the C version of rs17782313 was associated with an increase of 0.22 BMI units in adults (for a person of my height, 5 ft 3 in, that’s a little over a pound). In children, they found that this SNP had an even larger effect. Unlike the rare changes in MC4R that cause severe childhood obesity, 30 to 50% of the population has at least one copy of the C allele of rs17782313.

A second paper by Chambers et al., also published online Sunday in Nature Genetics, studied more than 14,000 Indian Asians and Europeans and found that a different SNP near MC4R, rs12970134, is associated with waist circumference. Each copy of the A version is associated with a 0.88 cm (0.3 in) increase in waist circumference. That means that on average, the waists of people with two copies of the A version of rs12970134 are 0.6 inches larger than the waists of people with two copies of the other version of the SNP. Talk about pinching an inch!

Fortunately for most of us, genes are only one player in our risk for obesity, as our behavior and environment can still play a large role in maintaining a healthy weight.

Calculating your BMI: You can calculate your own BMI using the following formula: multiply your weight in pounds by 0.454 to get your weight in kilograms. Then multiply your height in inches by .0254 to get your height in meters and square the result. Divide your weight in kilograms by your height in meters squared to get your BMI. A BMI less than 18.5 is considered underweight, between 18.5 and 24.9 normal, between 25 and 29.9 overweight, and above 30, obese.


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