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Previous Volume 348:1096-1103 March 20, 2003 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by List, J. F. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Obesity, a multifactorial disease caused by the interaction of genetic factors with the environment, is largely polygenic. A few mutations in these genes, such as in the leptin receptor (LEPR) gene and melanocortin 4 receptor (MC4R) gene, have been identified as causes of monogenic obesity.

Methods We sequenced the complete MC4R coding region, the region of the proopiomelanocortin gene (POMC) encoding the melanocyte-stimulating hormone, and the leptin-binding domain of LEPR in 469 severely obese white subjects (370 women and 99 men; mean [±SE] age, 41.0±0.5 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 44.1±2.0). Fifteen women and 10 men without a history of dieting or a family history of obesity served as normal-weight controls (age, 47.7±2.0 years; body-mass index, 21.6±0.4). Detailed phenotypic data, including information on body fat, resting energy expenditure, diet-induced thermogenesis, serum concentrations of leptin, and eating behavior, were collected.

Results Twenty-four obese subjects (5.1 percent) and one control subject (4 percent) had MC4R mutations, including five novel variants. Twenty of the 24 obese subjects with an MC4R mutation were matched for age, sex, and body-mass index with 120 of the 445 obese subjects without an MC4R mutation. All mutation carriers reported binge eating, as compared with 14.2 percent of obese subjects without mutations (P<0.001) and 0 percent of the normal-weight subjects without mutations. The prevalence of binge eating was similar among carriers of mutations in the leptin-binding domain of LEPR and noncarriers. No mutations were found in the region of POMC encoding melanocyte-stimulating hormone.

Conclusions Binge eating is a major phenotypic characteristic of subjects with a mutation in MC4R, a candidate gene for the control of eating behavior.

Source Information

From the Klinik Hirslanden, Zurich, Switzerland (R.B., N.P., F.F.H.); State University of New York Downstate Medical Center, Brooklyn (J.G.K.); Bioscientia, Ingelheim, Germany (K.-U.L.); and the Max Planck Institute for Molecular Genetics, Berlin, Germany (M.R.H.).

Address reprint requests to Dr. Horber at Klinik Hirslanden, Witellikerstr. 40, CH-8008 Zurich, Switzerland, or at genetics{at}obex.ch.

Full Text of this Article

Related Letters:

Binge Eating as a Phenotype of Melanocortin 4 Receptor Gene Mutations
Gotoda T., Herpertz S., Siffert W., Hebebrand J., Farooqi I. S., Yeo G. S., O'Rahilly S., Kral J. G., Lentes K.-U., Horber F.
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N Engl J Med 2003; 349:606-609, Aug 7, 2003. Correspondence

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