Mutation shows up in binge eaters. (Genetically Driven).

Overweight binge eaters are more likely to harbor a genetic mutation that disrupts brain signals governing satiety than are people of normal weight or obese people who don't regularly eat far more food than is needed to satisfy hunger, researchers report. The finding suggests that disruption of a particular gene underlies some binge eating, which until now has been classified as a psychiatric disorder. Another study shows that up to 6 percent of childhood obesity might stem from an inherited mutation in this gene.

Previous studies in animals associated binge eating with a mutation of the gene for a brain protein called melanocortin 4 receptor (MC4R). To test the effect of this gene defect on human behavior, Fritz F. Horber of the Hirslanden Clinic in Zurich and his colleagues obtained blood samples from 469 severely obese volunteers, average age 41. Genetic analysis of their blood revealed that 24 carried a mutated gene for MC4R.

These 24 individuals then completed a questionnaire on their eating habits. Next, the scientists identified 120 other people in the obese group who matched the mutation-carrying volunteers in age, sex, and weight. The researchers obtained blood samples and questionnaire answers from these volunteers and from 25 normal-weight people, average age 48, who had no history of dieting and no obesity in their families.

While all the obese people carrying a mutation in the gene for MC4R reported binge eating at least twice a week over 6 months, less than 15 percent of the other obese participants--and none of the normal-weight volunteers--did, the researchers report in the March 20 New England Journal of Medicine.

Although the cause of binge eating isn't fully understood, clues are emerging from studies of the body's molecular signals for satiety. MC4R proteins are receptors on brain cells that, when functioning properly, signal satiety. The new work provides evidence that when the gene for MC4R is mutated, the stop-eating sign doesn't go up, says Joel F. Hebener of the Howard Hughes Medical Institution and Harvard Medical School in Boston.

In the other study, which appears in the same journal issue, researchers sought to determine what proportion of obesity is attributable to a mutated gene for MC4R. Blood tests of 500 people with obesity that began before age 10 revealed that 29, or about 6 percent, carry mutations in the gene, according to Stephen O'Rahilly of Cambridge University in England and his colleagues.

Six of these 29 people showed a double dose of the mutated gene. These 6 individuals, who had been severely obese since childhood, had more body fat than the 23 who carried a single copy.

The two studies establish that "there are individuals out there who overeat not because they lack will power but because they have a physiological syndrome," says Roger D. Cone of the Oregon Health and Science University in Portland. "These people are genetically bound to overeat."

Pharmaceutical companies are devising drugs that could provide proper signaling to combat obesity in people with mutations in the gene for MC4R, Cone says.

Meanwhile, animal studies indicate that the signaling of satiety also relies on several other genes, Hebener says. By identifying mutations in them, scientists may provide drug companies with more targets for preventing obesity.