Binge Eating as a Phenotype of Melanocortin 4 Receptor Gene Mutations

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Abstract
Branson et al. (March 20 issue)1 found DNA sequence changes in the melanocortin 4 receptor (MC4R) gene in 24 of 469 severely obese subjects and confirmed binge eating in all the carriers examined. Of the 25 sequence changes identified, 11 (44 percent) were the Val103Ile change that my colleagues and I reported originally as a sequence variant that was not associated with obesity or obesity-related phenotypes.2 The notion that the Val103Ile change represents a variant of little physiologic significance has been supported by many functional and genetic studies.3 The only exception is a study that showed marginal evidence of an association between the Val103Ile change and lean phenotypes.4 Therefore, there is insufficient evidence to validate the inclusion of the Val103Ile change as an obesity-related MC4R mutation. The data presented by Branson et al., including the absence of a correlation between body fat and serum leptin levels in carriers of changes in MC4R, should be interpreted carefully. I would also point out that the Ser343Ser variant in the leptin receptor gene, which Branson et al. describe as a novel mutation, has been reported previously as a mere nonfunctional variant.5