Format

Send to

Choose Destination
Obesity (Silver Spring). 2013 Sep;21(9):E520-6. doi: 10.1002/oby.20459. Epub 2013 Jun 25.

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

Author information

1
Department of Statistics, Department of Biostatistics and Epidemiology, The Biostatistics Center, George Washington University, Rockville, Maryland, USA.

Abstract

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 Pinteraction < 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.

PMID:
23512951
PMCID:
PMC4023472
DOI:
10.1002/oby.20459
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center