Association Of Obesity-irelated And Metabolism-related Genetic Variants With Body Fat Distribution And Lipids Profiles

Background:Genome-wide association studies have revealed dozens of single-nucleotide polymorphisms(SNPs)associated with obesity and metabolic traits,but few studies have focused on the associations between these variations and body fat distribution in the Chinese.We thus aimed to identify loci affecting body fat distribution in Chinese adults.Method:Forty-three previously identified obesity-related SNPs and 11 metabolism-related SNPs were analyzed.Genotyping of these SNPs was performed among 974 Chinese adults aged 18-79 years.The body fat distribution represented by body fat percentage,trunk fat percentage,and android and gynoid fat percentages was estimated using dual-energy X-ray absorptiometry.Sex-stratified multiple linear regression was used to assess whether these SNPs were associated with body fat distribution and lipid profiles in additive,dominant,and recessive models.Results:A total of 12 SNPs encompassing 9 loci were associated with body mass index(BMI)after adjustment for age,smoking,alcohol use,and physical activity(all P<0.05),consisting of the nine obesity-related variants(in or near KCTD15,MC4R,NUDT3,MTCH2,TMEM18,BDNF)and three metabolism-related variants(in or near UCP1,FADS,FNDC5).Five SNPs showed the significant association with BMI only among men,and seven SNPs showed the association only among women.After adjustment for age,BMI and lifestyle factors,18 SNPs encompassing 12 loci showed evidence of an association(all P<0.05)with regional fat percentages in the sex-specific analysis,in or near FTO,MC4R,RPL27A,QPCTL,ADRB2,THEM18,MTCH2,KCTD15,BDNF,UCP1,FADS,ATP2B1 In men,11 SNPs were observed to be associated with at least one fat distribution indicator,comprising eight obesity-related variants.In women,13 SNPs reached a significant association,also comprising eight obesity-related variants.Five SNPs were observed to be associated with fat distribution in both sexes,of which three were metabolism-related variants.Furthermore,twenty-six SNPs encompassing 15 loci were associated with lipids profiles(in or near ADRB2,BDNF,FGF5,FTO,LDLR,MITF3,NEGRI,NUDT3,RPL27A,SEC16B,TMEM18)and five SNPs were observed to be associated among both gender.Conclusion:Several SNPs were identified to be associated with BMI and body fat distribution and lipid profiles among adults.These findings demonstrate that different genetic factors contribute to fat distribution in the two sexes.Future studies are warranted to identify the genetic factors mediating the gender difference in body fat distribution.