Gene to blame in rare cases of extreme obesity

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Changes to a gene involved in the regulation of body weight may contribute to weight gain in a very small number of obese individuals, new research reports.

Investigators found that people with these changes, or mutations, to the gene encoding the melanocortin-4 receptor (MC4R) were much heavier than people who did not carry a mutation.

“These particular mutations seem to be associated with obesity,” study author Dr. Johannes Hebebrand of Philipps-University in Marburg, Germany told AMN Health.

However, don’t start blaming your genes for your weight just yet: Hebebrand noted that MC4R mutations are very rare, and only between 2 and 3 percent of very obese people carry them.

Previous research has shown that MC4R may play a significant role in maintaining body weight. For instance, the receptors are abundant in the hypothalamus, a part of the brain that helps control appetite. Investigators have also found that mice that are missing MC4 receptors overeat and become obese.

To investigate how much weight MC4R mutation holders tend to put on, Hebebrand and his colleagues measured the body mass index of 181 relatives of very obese children known to carry a MC4R mutation, and noted whether they, too, were mutation carriers.

Researchers calculated the subjects’ body mass index (BMI), a ratio of weight-to-height. A BMI of over 25 is considered to be overweight. A BMI of 30 or above is obese, while 40 or higher is considered very obese.

Reporting in the Journal of Medical Genetics, Hebebrand and his colleagues found that men who carried a MC4R gene mutation were an average of 5 BMI units heavier than male non-carriers. In females, MC4R mutations increased weight by an average of 10 BMI units.

Hebebrand noted that not all mutation carriers were obese, suggesting that carrying a mutation in the MC4R gene does not always lead to obesity. However, he noted that even non-obese mutation carriers tended to weigh more than non-carriers.

Since mutation carriers have a predisposition to obesity, it may be somewhat harder for them to shed pounds through diet and exercise - but not impossible, Hebebrand noted.

He explained that other genes seem to also play a role in obesity, but MC4R appears to have more potential mutations.

SOURCE: Journal of Medical Genetics, October 2004.

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