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Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program.

ABSTRACT: To assess associations and genotype × treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits.Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment.The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all Pinteraction < 0.05).This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.

SUBMITTER: Pan Q 

PROVIDER: S-EPMC4023472 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other

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Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program.

Pan Qing Q   Delahanty Linda M LM   Jablonski Kathleen A KA   Knowler William C WC   Kahn Steven E SE   Florez Jose C JC   Franks Paul W PW  

Obesity (Silver Spring, Md.) 20130625 9

<h4>Objective</h4>To assess associations and genotype × treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits.<h4>Design and methods</h4>Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed to  ...[more]