Abstract
BackgroundAdiponectin Q is a hormone that modulates several metabolic processes and contributes to the suppression of biochemical pathways leading to metabolic syndrome. Hence, polymorphic changes in the adiponectin Q (ADIPOQ) gene are likely to contribute to metabolic disorders, and consequently lead to atherosclerosis. In the present study, we performed a population-based association study for 8 SNPs in 4646 Saudi individuals (2339 CAD cases versus angiographed 2307 controls) by real-time PCR.MethodsLinkage analysis was done by the Affymetrix Gene Chip array, sequencing by the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry with the Applied Biosystem real-time Prism 7900HT Sequence Detection System.ResultsThe rs2241766 (TG + GG) [Odds ratio(95% Confidence Interval = 1.35(1.01-1.72); p = 0.015] and rs9842733A > T [1.48(1.01-2.07); p = 0.042] were associated with hypertension [HTN; 3541 cases vs 1101 controls), following adjustment for the presence of other cardiovascular risk traits. The rs2241766 (TG + GG) was further implicated in harbouring of low high density lipoprotein levels (LHDL; 1353 versus 2156 controls) [1.35(1.10-1.67); p = 0.005], but lost its association with obesity after the adjustment for confounders. Besides, low high density lipoprotein was also linked with rs6444174 (TC + CC) [1.28(1.05-1.59)]. On the other hand, while initial univariate logistic regression analysis pointed to rs1063537 C > T (p = 0.010), rs2082940 C > T (p = 0.035) and rs1063539 G > C (p = 0.035) as being associated with myocardial infarction, significance levels of these relationships were diminished following adjustment for the influence of confounding covariates. Interestingly, haplotyping showed that an 8-mer haplotype GTGCCTCA and several of its derivatives constructed from the studied SNPs were commonly implicated in MI (χ2 = 4.12; p = 0.042), HTN (χ2 = 6.40; p = 0.011) and OBS (χ2 = 5.18; p = 0.023).ConclusionThese results demonstrate that the ADIPOQ 3′UTR harbours common susceptibility variants for metabolic risk traits and CAD, pointing to the importance of this region in atherosclerosis disease pathways.
Highlights
Adiponectin Q is a hormone that modulates several metabolic processes and contributes to the suppression of biochemical pathways leading to metabolic syndrome
In a preliminary genome-wide linkage study involving a Saudi family consisting of 11 individuals, with predominant heterozygous familial hypercholesterolemia (HFH), we identified using the Affymetrix Gene Chip 250 sty1 mapping array, several genomic loci that were linked to both early onset of coronary artery disease (CAD) and HFH (Additional file 1)
Linkage analysis and gene sequencing The sequencing of all exons, exon-intron junctions, the promoter as well as the 3′-UTR of the adiponectin Q (ADIPOQ) gene in the HFH family members and 200 other individuals from the general population led to the discovery of various single nucleotide changes
Summary
Adiponectin Q is a hormone that modulates several metabolic processes and contributes to the suppression of biochemical pathways leading to metabolic syndrome. In a preliminary genome-wide linkage study involving a Saudi family consisting of 11 individuals, with predominant heterozygous familial hypercholesterolemia (HFH), we identified using the Affymetrix Gene Chip 250 sty mapping array, several genomic loci that were linked to both early onset of CAD and HFH (Additional file 1) These loci included one on chromosome 3, which harbours the ADIPOQ gene. Sequencing the gene in the family members and 200 individuals from the general population revealed the ADIPOQ gene as being extensively polymorphic in the Saudi population This led to the notion of interactions involving some of the metabolic risk traits and the ADIPOQ gene as a triggering factor for both early and late onset of atherosclerosis. We set out to investigate the likelihood of some of the ADIPOQ variants we identified in the initial linkage experiment, conferring risk for cardiovascular and metabolic risk traits, focusing on the involvement of the 3′UTR of the gene
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