Date Published: January 12, 2017
Publisher: Public Library of Science
Author(s): Jie-Yun Song, Qi-Ying Song, Shuo Wang, Jun Ma, Hai-Jun Wang, Yang-Ching Chen.
Effects of MC4R variants in previous Chinese population studies were inconsistent. Gene-environment interactions might influence the effect of MC4R variants on obesity, which was still unclear. We performed the study to clarify the association of variants near MC4R gene with obesity-related phenotypes and gene-environment interactions in Chinese children and adolescents. Two common variants (rs12970134 and rs17782313) near MC4R were genotyped in 2179 children and adolescents aged 7–18 years in Beijing of China. Associations between the variants and obesity-related phenotypes together with gene-environment interactions were analyzed. The A-alleles of rs12970134 were nominally associated with risk of overweight/obesity (Odds Ratios (OR) = 1.21, 95%CI: 1.03–1.44, P = 0.025) and BMI (β = 0.33 kg/m2, 95%CI: 0.02–0.63, P = 0.025), respectively. The rs12970134 was also associated with HDL-C (β = -0.03mmol/L per A-allele, 95%CI: -0.05, -0.01, P = 0.013) independent of BMI. In the further analysis, we found the significant interaction of rs12970134 and physical activity/sedentary behaviors on BMI (Pinteraction = 0.043). The rs12970134 was found to be associated with BMI only in children with physical activity<1h/d and sedentary behaviors ≥2h/d (BMI: β = 1.27 kg/m2, 95%CI: 0.10–2.45, P = 0.034). The association was not detected in their counterparts with physical activity≥1h/d or sedentary behaviors <2h/d. We identified the effect of MC4R rs12970134 on overweight/obesity and BMI, and we also found physical activity and sedentary behaviors modified the association between the rs12970134 and BMI in Chinese children and adolescents.
The melanocortin-4 receptor (MC4R) is primarily expressed in the central nervous system and a part of melanocortinergic pathway that regulates food intake and controls energy homeostasis . The MC4R homozygous knock-out mice had maturity onset obesity, hyperphagia, increased linear growth, hyperinsulinemia, and hyperglycemia, reduced metabolic rate . The role of the central melanocortin system on adiposity by controlling nutrient partitioning and lipid metabolism independent of nutrient intake was reported .
In the present study, we validated the effect of rs12970134 on BMI and risk of overweight/obesity in Chinese children. Additionally, we found the effect could be modified by dietary factors, physical activity and sedentary behaviors.
In conclusion, we found rs12970134 variant was nominally associated with BMI, risk of overweight/obesity, hip circumstance and body fat percentage. The rs12970134 was also associated with HDL-C independent of BMI. Physical activity and sedentary behaviors were identified in modifying the effect of rs12970134 variant on BMI and risk of overweight/obesity in Chinese children. The study results help to clarify the effects of MC4R genetic variants on childhood obesity.