Gene variant increases risk of obesity

19 April 2007

People carrying one or two copies of a specific variant of a gene called FTO are heavier on average and have a higher body mass index than those who do not carry the variant, according to British researchers [Frayling, TM et al. (2007) Science Apr 12; Epub ahead of print]. The FTO gene, whose function is so far unknown, was originally identified in a study aimed at finding genes associated with type II diabetes, by comparing 500,000 single nucleotide polymorphisms (SNPs) in 1924 people with diabetes and 2938 people without the disease. While some diabetes-associated genes are involved in insulin metabolism, the association between the FTO SNP and diabetes appeared to be mediated by an effect on body mass index (BMI), prompting the researchers to look for the variant in other study populations – totalling nearly 39,000 individuals – in which BMI had been measured. The association between the FTO SNP and BMI held up strongly in two diabetes populations, nine cohorts of white European adults, and two studies of European children.

On average, people with one copy of the FTO SNP (about half the population) had a 30% increased risk of being obese compared to those with no copies. People with two copies had a 70% increased risk, and were on average 3 kg heavier than otherwise similar people who did not carry the variant. 

Comment: The association between the FTO gene and body mass index appears to be robust, and is strengthened by the fact that it has been confirmed in several different populations. It is hoped that further studies on the FTO gene will reveal its function and shed light on how a single base change in its sequence can have such a dramatic effect on weight gain.

It is important to keep in mind, however, that the second law of thermodynamics still applies: weight gain results from consuming more calories than are expended. Perhaps it may soon be possible to understand why some people are more prone to this imbalance than others.      

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