Common gene variants linked to obesity

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Researchers have identified new genetic variants that influence the risk of obesity and insulin resistance, a precursor to diabetes, according to findings from two studies published online this week.

In the first of the two genome-wide association studies, a research team headed by Dr. Ruth J. F. Loos, from Addenbrooke’s Hospital in Cambridge UK, analyzed data from 16,876 people of European descent.

The investigators not only confirmed prior research linking variants in the FTO gene with obesity, but they also identified a strong association with genetic variants near the MC4R gene. The MC4R gene regulates energy levels in the body by influencing how much we eat and how much energy we expend or conserve. Mutations in this gene are the most common genetic cause of severe obesity that runs in families. 

The findings by Loos and colleagues, which were later confirmed in 60,352 adults and 5988 children, showed that the presence of the MC4R risk variant increased the odds that a child would be obese by up to 30 percent. An analysis of data from 660 families revealed that “over transmission” of the risk variant was common among obese offspring.

“Several groups had shown that rare, highly disruptive variants in the MC4R gene were responsible for very severe, genetic forms of obesity: this collaboration (by many international groups) has uncovered more common variants that affect more people,” Loos said in a statement.

In the second study, an investigation of 318,237 single letter changes, or SNPs, in the DNA of over 14,000 subjects of Indian Asian and European descent, Dr. Jaspal S. Kooner, from Imperial College London, and colleagues linked a gene sequence variant near the MC4R gene with increased waist circumference and a tendency to become insulin resistant, which can lead to type 2 diabetes.

Two copies of the risk variant added roughly 2 cm to waist circumference and increased insulin resistance by about 10 percent, the results show.

“A better understanding of the genes behind problems such as diabetes and cardiovascular disease means that we will be in a good position to identify people whose genetic inheritance makes them most susceptible,” Kooner said in a written statement.

“We can’t change their genetic inheritance. But we can focus on preventative measures, including life-style factors such as diet and exercise, and identifying new drug targets to help reduce the burden of disease,” Kooner added.

SOURCE: Nature Genetics, May 4, 2008.

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