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Variation at the melanocortin 4 receptor gene and response to weight‐loss interventions in the diabetes prevention program
Author(s) -
Pan Qing,
Delahanty Linda M.,
Jablonski Kathleen A.,
Knowler William C.,
Kahn Steven E.,
Florez Jose C.,
Franks Paul W.
Publication year - 2013
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20459
Subject(s) - psychological intervention , melanocortin , diabetes mellitus , medicine , melanocortin 4 receptor , weight loss , endocrinology , variation (astronomy) , receptor , bioinformatics , obesity , biology , physics , psychiatry , astrophysics
Objective To assess associations and genotype × treatment interactions for melanocortin 4 receptor ( MC4R ) locus variants and obesity‐related traits. Design and Methods 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. Results 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 P interaction < 0.05). Conclusion 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.