Common gene variants linked to obesity (Reuters)

NEW YORK (Reuters Health) - Researchers have identified newgenetic variants that influence the risk of obesity and insulinresistance, a precursor to diabetes, according to findings fromtwo studies published online this week.

In the first of the two genome-wide association studies, aresearch team headed by Dr. Ruth J. F. Loos, from Addenbrooke'sHospital in Cambridge UK, analyzed data from 16,876 people ofEuropean descent.

The investigators not only confirmed prior research linkingvariants in the FTO gene with obesity, but they also identifieda strong association with genetic variants near the MC4R gene.The MC4R gene regulates energy levels in the body byinfluencing how much we eat and how much energy we expend orconserve. Mutations in this gene are the most common geneticcause of severe obesity that runs in families.

The findings by Loos and colleagues, which were laterconfirmed in 60,352 adults and 5988 children, showed that thepresence of the MC4R risk variant increased the odds that achild would be obese by up to 30 percent. An analysis of datafrom 660 families revealed that "over transmission" of the riskvariant was common among obese offspring.

"Several groups had shown that rare, highly disruptivevariants in the MC4R gene were responsible for very severe,genetic forms of obesity: this collaboration (by manyinternational groups) has uncovered more common variants thataffect more people," Loos said in a statement.

In the second study, an investigation of 318,237 singleletter changes, or SNPs, in the DNA of over 14,000 subjects ofIndian Asian and European descent, Dr. Jaspal S. Kooner, fromImperial College London, and colleagues linked a gene sequencevariant near the MC4R gene with increased waist circumferenceand a tendency to become insulin resistant, which can lead totype 2 diabetes.

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

"A better understanding of the genes behind problems suchas diabetes and cardiovascular disease means that we will be ina good position to identify people whose genetic inheritancemakes them most susceptible," Kooner said in a writtenstatement.

"We can't change their genetic inheritance. But we canfocus on preventative measures, including life-style factorssuch as diet and exercise, and identifying new drug targets tohelp reduce the burden of disease," Kooner added.

SOURCE: Nature Genetics, May 4, 2008.