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Background  Little is known about the correlation between the melanocortin 4 receptor gene ( MC4R ) single nucleotide polymorphisms (SNPs) and the risk of obesity. This research sought to test the  MC4R  rs17782313, rs476828 and rs12970134 SNPs, their haplotypes and gene-environment interactions on the risk of obesity in the Maonan ethnic group, an isolated minority in China.    Methods  A case-control study comprised of 1836 participants (obesity group, 858; and control group, 978) was conducted. Genotypes of the three SNPs were determined by the next-generation sequencing (NGS) technology.    Results  The genotypic frequencies of the three SNPs were different between the obesity and control groups ( P  <  0.05 for all). The minor allelic frequency of the  MC4R  rs17782313C, rs476828C and rs12970134A was higher in obesity than in control groups (13.8% vs. 8.3%,  P  <  0.001, 17.1% vs. 10.9%,  P  <  0.001; and 15.5% vs. 11.5%,  P  <  0.001; respectively). Additionally, the dominant model of rs17782313 and rs476828 SNPs revealed an increased morbidity function on the risk of obesity ( P  <  0.05). A correlation between SNP-environment and the risk of obesity was also observed. The rs17782313C-rs476828C-rs12970134A haplotype was associated with high risk of obesity (OR = 1.796, 95% CI = 1.447–2.229), whereas the rs17782313T-rs476828T-rs12970134G and rs17782313T-rs476828T-rs12970134A haplotypes were associated with low risk of obesity (OR = 0.699, 95% CI = 0.586–0.834 and OR = 0.620, 95% CI = 0.416–0.925; respectively). The interactions between haplotype and waist circumference on the risk of obesity were also noted.    Conclusions  We discovered that the  MC4R  rs17782313, rs476828 and rs12970134 SNPs and their haplotypes were associated with the risk of obesity in the Chinese Maonan population.

The MC4R SNPs, their haplotypes and gene-environment interactions on the risk of obesity