Abstract 468: The 3’-utr of Adiponectin Q Gene Harbours Common Susceptibility Variants and Haplotypes for Metabolic Risk Traits

Abstract

Adiponectin (ADIPOQ) is a hormone that modules several metabolic processes and is thought to contribute to the suppression of the metabolic derangements that may lead to metabolic syndrome. In the present study, we performed a population-based association study by real-time PCR for 8 SNPs in a total of 4650 Saudi individuals harbouring various metabolic risk traits. Among these SNPs, rs1063537 T allele [Odds ratio(95% Confidence Interval = 1.16(1.04-1.30); p=0.011], rs1063537 CT+TT genotypes [1.16(1.02-1.33); p=0.024], rs2082940 T [1.12(1.01-1.24); p=0.035] and CT+TT [1.37(1.02-1.83); p=0.039] as well as rs1063539 C [1.13(1.01-1.20); p=0.035] conferred risk for myocardial infarction (MI; 3060 cases vs 1590 controls). The rs2241766 T [1.26(1.02-1.54); p=0.028], rs6773957 AG+GG [1.15(1.01-1.31); p=0.030], rs4686804 CT+ TT [1.15(1.01-1.30); p=0.033] were associated with obesity (1757 vs 2576). The rs2241766 T was likewise implicated in low high density lipoprotein levels (lHDL; 1926 vs 2393) [1.29(1.06-1.58); p=0.013] and primary hypertension (HTN; 3533 cases vs 1590) [1.25(1.01-1.55); p=0.039], while rs9842733 T was associated with HTN [1.44(1.03-2.01); p=0.032] and hypercholesterolaemia (hChol; 1681 vs 2739) [1.32(1.01-1.72); p=0.043]. An 8-mer haplotype GTGCCTCA constructed from the 8 SNPs and its derivatives were commonly implicated in MI (Χ 2 =4.12; p=0.042) and HTN (Χ 2 =6.40; p=0.011) and obesity (Χ 2 =5.18; p=0.023). On the other hand, hChol levels were associated with the 5-mer TTATT (Χ 2 = 9.56; p = 0.002) and its 4-mer derivative TTAT (Χ 2 = 7.56; p=0.006) while lHDL was linked with the TCCA (Χ 2 = 5.06; p = 0.025). These results demonstrate that the 3’UTR of the ADIPOQ gene harbours common susceptibility variants and haplotypes for the important determinants of metabolic syndrome and cardiovascular risk traits, possibly pointing to a common underlying pathway to coronary artery disease.