Sex-specific genetic association of brain and muscle Arnt-like protein-1 (BMAL1) and obesity in Chinese youth.

Background: The circadian clock gene brain and muscle Arnt-like protein-1 (BMAL1) regulates energy metabolism, adipocyte proliferation and differentiation, glucose metabolism, and other functions. This study aimed to examine the association of potential polymorphisms in BMAL1 with obesity among Chinese youth.

Methods: A total of 2973 participants were included in this study. According to the body mass index obesity standard of China, 208 subjects were defined as experiencing general obesity. According to the waist-to-hip ratio obesity standard, 335 participants were defined as experiencing central obesity. Four single nucleotide polymorphisms (SNPs) (rs9633835, rs6486121, rs7107287, and rs12364562) were genotyped using TaqMan probe techniques.

Results: There was no significant difference in the either genotypic or allelic frequencies between the non-general and general obesity groups, while a positive association was observed between BMAL1 rs6486121 variant and central obesity risk (CC＋CT vs. TT: OR:2.139, 95% CI:1.164-3.930; P = 0.014) after adjusting for covariates. Stratification analyses revealed significant associations with central obesity risk for rs6486121 polymorphism in women according to the additive model (CC vs. CT vs. TT: OR：1.409; 95 % CI: 1.029-1.930; P = 0.032). Haplotype analysis showed that only paired haplotypes, including rs9633835G with rs6486121T, had a significant effect on central obesity with OR (95%CI) was 1.035 (1.011-1.060) and P = 0.004.

Conclusion: our findings suggest that BMAL1 polymorphisms are significantly associated with central obesity and sex-specific genetic effects on BMAL1-mediated genetic susceptibility to obesity.