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Studies Say Genes Govern Overeating

For obese people, 'it's not their fault,' researcher says

WEDNESDAY, March 19, 2003 (HealthDayNews) -- Researchers have found genetic mutations that contribute to obesity by influencing how people eat, and they think these changes may be much more common than once thought.

Specifically, two articles in the March 20 issue of The New England Journal of Medicine show that mutations in the melanocortin 4 receptor (MC4R) lead to uncontrolled overeating and to binge eating.

"It's a great example of behavioral genetics," says Dr. Michael Devlin, clinical co-director of the Eating Disorders Research Unit at the New York State Psychiatric Institute in New York City. "This gene influences behavior. We tend to think in terms of how biology [and] your metabolism are influenced by genes, but behavior doesn't seem like it should be. This seems to be a clear example."

Scientists have long known that, along with diet and exercise, genes contribute to the current epidemic of obesity. In fact, some 50 percent to 90 percent of variation in body mass index among humans is considered to be heritable, say the study authors. So far, about 30 different mutations in MC4R have been linked to obesity.

The authors of the first study looked at 500 patients with severe childhood-onset obesity and found that 5.8 percent had "functionally important" mutations in the MC4R gene.

"This mutation is really very strongly associated with obesity syndrome," says Dr. Joel F. Habener, co-author of an editorial appearing in the same issue of the journal. "This particular MC4R mutation is out of the rare category. It's in the substantial category and approaching 6 percent. It's out there and it's not just trivial."

The authors of the second study looked at 469 severely obese people and 25 controls and found that 5.1 percent of the obese participants and 4 percent of the controls had MC4R mutations, including five previously unknown ones. All obese subjects with a mutation reported binge eating versus only 14.2 percent of the obese subjects without mutations.

Binge-eating disorder, which is characterized by eating unusually large quantities of food, appears then to be caused by an MC4R mutation, the study authors state.

Although the mutations could present a target for future drug therapies, the more immediate benefit is that certain obese people no longer need to blame themselves for reckless eating.

Although the causes of obesity remain complex and multifaceted, physicians who are treating very obese people have a reason to elicit the patient's history of binge eating and ask detailed questions about how and why they overeat. "Based on these studies, there's a high probability that this would be due to the mutation in this receptor," Habener says. "At least they would then have the assurance that this is not their fault, that they're not fat because they can't control themselves. It's not their fault."

Yet another study suggests obesity may be a collection of many diseases, and not just one unto itself. Researchers at Rosetta Inpharmatics of Kirkland, Wash., found that extremely overweight mice had a "hot spot" of obesity-related genes on chromosome 2. They report their findings in the March 20 issue of Nature.

More information

For more on obesity, visit the American Obesity Association or the North American Association for the Study of Obesity.

SOURCES: Michael Devlin, M.D., clinical co-director, Eating Disorders Research Unit, New York State Psychiatric Institute, New York City; Joel F. Habener, M.D., director, laboratory of molecular endocrinology, Massachusetts General Hospital, Boston, and investigator, Howard Hughes Medical Institute, Chevy Chase, Md.; March 20, 2003, The New England Journal of Medicine; March 20, 2003, Nature
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