Genetic Mutation Associated With Binge Eating

Rrecent multinational study strongly linked irregularities in the melanocortin 4 receptor (MC4R) gene—which many previous studies have related to eating behavior and obesity—to binge eating disorder.

Researchers from Switzerland, Germany, and the United States concluded that coding sequence variation, or mutations, in MC4R is a likely cause of binge eating. In their study of 469 severely obese subjects and 25 normal weight controls, 100 percent of people identified with such variations in MC4R met the criteria for binge eating, compared to 14.2 percent of other obese subjects and none of the normal-weight subjects without the MC4R variants.

As technologies to explore the human genome continue to advance rapidly, the genetics of obesity have become a topic of burgeoning interest. In animal and human studies, MC4R has been found to have an important role in the regulation of body weight, manufacturing a protein that stimulates appetite in the hypothalamus, the part of the brain that regulates hunger. MC4R mutations have been linked to increased food intake and extreme and early onset obesity.

But the association these researchers have suggested needs to be replicated in other studies before the information can be applied in any way, caution other scientists. The authors of an editorial that accompanied the article describing the study noted that the current findings differ from an earlier study that identified binge eating in only 5 percent of people with MC4R mutations.

In this study, the MC4R variations were seen in about one-fifth of the binge eaters, but it is unclear whether the irregularities have any functional effect. The types of mutations found in 19 of the 24 subjects “do not affect the function of the receptor in biochemical studies,” said Rudolph L. Leibel, M.D., head of the Division of Molecular Genetics of the Columbia University College of Physicians and Surgeons. “If we don’t count these subjects, only 4 percent of the binge eaters had significant MC4R variants. This is no higher than the rate that has been previously described for individuals with severe, early onset obesity.”

"As technologies to explore the human genome continue to advance rapidly, the genetics of obesity have become a topic of burgeoning interest."

However, Dr. Leibel added, “it would be fascinating if a behavior as complex as binge eating could be attributed to a single gene.”

Binge-eating disorder is described as rapid consumption of a large amount of food accompanied by a sense of loss of control over eating, and occurring at least twice a week for 6 months or longer. Binging causes a person to feel embarrassed, guilty, or depressed. An estimated 4 million Americans meet the diagnosis for binge eating, and most—but not all—are obese. The prevalence of binge-eating disorder in subjects who are obese varies widely from study to study, but is estimated to range from less than 5 percent in community samples to more than 30 percent in severely obese persons seeking specialized treatment; the prevalence in subjects who are not obese is less than 3 percent.1 In this study looking at MC4R and binging, diagnostic criteria for binge-eating disorder were confirmed by a dietitian, a psychologist, and a physician specializing in obesity.

The authors of the study speculated that melanocortin agonist, now under development, could turn out to be an effective pharmaceutical treatment for binge eating disorder.
Researchers also compared prevalence of binge eating and DNA coding sequence variations of other genes that are associated with appetite and found no significant differences between people with and without such variations. While some single-gene mutations have been identified as a cause of obesity, these occur very rarely.

The study was published in the March 20, 2003 New England Journal of Medicine. s