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Variation at the Melanocortin 4 Receptor Gene and Response to Weight-Loss Interventions in the Diabetes Prevention Program
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2013 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 9, E520-E526 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To assess associations and genotype x 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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013. Vol. 21, no 9, E520-E526 p.
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Nutrition and Dietetics Endocrinology and Diabetes
URN: urn:nbn:se:umu:diva-82828DOI: 10.1002/oby.20459ISI: 000325426600026OAI: diva2:663331
Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2015-12-16Bibliographically approved

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