Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population

Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 × 10(-5) and 6.54 × 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 × 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 × 10(-8) and 4.43 × 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 × 10(-4) and 4.65 × 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.