Effect of the melanocortin-3 receptor C17A and G241A variants on weight loss in childhood obesity

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The central melanocortin system is critical for the long-term regulation of energy homeostasis. Melanocortin-3 receptor (MC3R) knock-out mice, despite being hypophagic, have increased fat mass and higher feed efficiency than do their wild-type littermates. The aim was to evaluate whether, in childhood obesity, MC3R variants are associated with changes in fatness reduction as a consequence of a weight-reduction program. No new mutations were found. Two previously described polymorphisms, C17A (Thr6Lys) and G241A (Val81Ile), were observed in 20 patients in almost complete linkage disequilibrium. No significant differences in BMI z scores were observed at baseline of the weight-loss program between the genotypes; however, at follow-up, heterozygotes showed a significantly higher BMI z score (P = 0.03). When the patients were divided according to the amount of weight lost, a higher prevalence of heterozygotes was observed among subjects who lowered their BMI z score <1.5 (P = 0.03). These results suggest a gene-diet interaction between the MC3R C17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity.

Keywords: MC3R gene polymorphism childhood obesity weight loss BMI z score