Melanin-concentrating hormone receptor 1 polymorphisms are associated with components of energy balance in the Complex Diseases in the Newfoundland Population: Environment and Genetics (CODING) study

Background: The melanin-concentrating hormone receptor 1 (MCHR1) is a G protein coupled receptor that regulates energy balance and body composition in animal models. Inconsistent effects of MCHRI polymorphisms on energy homeostasis in humans may partly be attributable to environmental factors. Objectives: We examined the effect of 4 single nucleotide polymorphisms (rs133073, rs133074, rs9611386, and rs882111) in the MCHRI gene on body composition as well as energy-related lifestyle factors (diet and physical activity). We also examined the effect of gene-lifestyle interactions on body composition. Design: A total of 1153 participants (248 men and 905 women) from the cross-sectional Complex Diseases in the Newfoundland Population: Environment and Genetics (CODING) study were genotyped by using probe-based chemistry validated assays. Diet and physical activity were estimated by using validated frequency questionnaires, and body composition was assessed by using dual-energy X-ray absorptiometry. Results: Three polymorphisms (rs9611386, rs882111, and rs133073) were associated with differences in body-composition measurements (all P < 0.05). There was an interaction between rs9611386 and carbohydrate intake on total mass and waist circumference (both P <= 0.01). There was also an interaction between rs9611386 and body mass index categories (normal weight, overweight, and obese) on energy intakes (P = 0.02). A similar interaction was shown with rs882111 (P = 0.02). Interactions were also observed between each of these polymorphisms (rs96 11386, rs882111, and rs133073) and physical activity score on body-composition measurements (all P < 0.05). Conclusion: These findings suggest that polymorphisms in the MCHRI gene are associated with differences in body composition and interact with physiologic and energy-related lifestyle factors.