Adiponectin Gene Polymorphisms and Type 2 Diabetes among

Background: Adiponectin is the most abundant circulating adipokine in human that regulates insulin actions. Association of adiponectin gene variations with type 2 diabetes (T2DM) has been reported albeit predominantly in non-Asian populations. Additionally, proof of variant functionality beyond statistical association is often unavailable. We studied six common (minor allele frequency ≥0.05) adiponectin single nucleotide polymorphisms (SNPs) in Singaporean Chinese adults with follow-up functional genetic experiments. Methods: In a case-control study (N=588), genotyping of six common adiponectin haplotype tagging SNPs [-3964A>G(rs822396), +45T>G(rs2241766), 276C>A(rs1501299), 973G>A(rs3774262), 4551G>C(rs1063539) and 5852G>A(rs6444175)] was performed using Taqman genotyping assay. Allele-dependent differential efficiency of mRNA expression was tested with quantitative real time PCR using human subcutaneous and omental adipose tissues. Results: Distributions of genotypes for all SNPs among controls were consistent with Hardy-Weinberg Equilibrium. Single locus, genotyped-based analysis suggested borderline significant ( P=0.07) association between an exon2 coding-synonymous +45T>G(rs2241766) and T2DM. We demonstrated that the relative mRNA expression of adiponectin gene was ~80% lower among carriers of minor G allele in human subcutaneous adipose tissue (N=43, p G(rs2241766) and T2DM among Singaporean Chinese adults. Functional experiments in both human subcutaneous and omental adipose tissue suggested that polymorphisms in +45T>G(rs2241766) may be associated with differential allelic expression.