Oprm1 Gene Polymorphism And The Uyghur Population Obesity Association Studies

Objective:to explore the associations of Mu-opioid receptor(OPRM1) gene with Body Mass Index(BMI) and obesity related clinical quantitative traits.Methods:A population based association study was carried out in a Chinese Minority group-Uyghur population live in Xinjiang district.In total,860 Uyghur subjects were randomly recruited in our research.From the Hapmap database(http://www.hapmap.org/cgi-perl/gbrowse/hapmap B35/),10 ten tagging single nucleotide polymorphisms(tSNPs) were chosen for this association study.At the first stage,the differences of BMI and other obesity related quantitative traits,such as waist hip ratio,glucose,triglyceride,and cholesterol levels,were compared among different genotypes.Then, association analyses with the alleles and the genotypes in all these ten tSNPs in OPRM1 gene with obesity,defined by BMI(case group:BMI≥28kg/m²; control group:BMI18.5～24kg/m²) were performed.Similar analysis with haplotypes of these tSNPs was also performed.Results:Genotypes of rs1799971 in exon1,and rs514980 and rs7773995 in intron1 were significant associated with the BMI.rs1799971 is a missense mutation(Asn40Asp).The mean of BMI significantly decreased by the copy of minor allele carriers of rs1799971(p=0.005) which is a non-synonymous functional polymorphism,and the BMI significantly increased by the copy of minor allele carriers of rs514980(p=0.010) and rs7773995(p=0.005).The significance still remained after controlling for covariate age and sex.However, no significance was found in other clinical traits.Subjects were subsequently divided into case(BMI≥28kg/m²) and control group(BMI18.5～24kg/m²). Significantly associations with obesity were also observed at rs1799971 (P₁=0.069;p₂=0,022),rs514980(p₁=0.029;p₂=0.0067) and rs7773995 (p₁=0.039;p₂=0.011),regardless of controlling for covariates age and gender or not.The stronger evidence for association was found under the additive model for three SNPs.The per-allele OR of the minor allele for obesity was 0.75(95% CI 0.58-0.96,p=0.023) for 1799971,1.68(95%CI 1.14-2.49,p=0.009) for rs514980,and 1.80(95%CI 1.14-2.85,p=0.012) for rs7773995,resectively. Conclusions:Our observations firstly give the evidence that OPRM1 gene polymorphism might be involved in the development of obesity in Uyghur population,and further study needs to be conducted.