The 3′-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits

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.

Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort

“…A recent study conducted in Saudi population showed this SNP to be associated only with low HDL-C serum levels. Although the authors did not report the rare allele frequency for this polymorphism in their population [ 43 ], demographic data from Saudi Arabia shows 10 % of Afro-Asian ancestry which could explain the presence of this allele in this ethnic group. We hypothesized that this African ancestry-specific allele might be conferring a metabolic protection through higher adiponectin levels and an increased homeostasis of fat deposition in subjects within a normal weight range but that protection or metabolic advantage is susceptible to modification under an obese environment.…”

“…Although this ADIPOQ variant is a silent polymorphism located in intron 1, and based on reports from the Alibaba 2.1 program, it is not involved in any putative transcription binding site [ 58 ]. It has recently been suggested that some organisms possess the ability to selectively use certain codons for transcriptional selection or translational and RNA stability [ 43 ], conferring this SNP a potential regulatory activity.…”

Association of the Variants of Nucleotide Sequence of the Gene Adipoq With Plasmatic Level of Adiponectin, the Grade of Coronary Atherosclerosis Severity and Rate of Cardiovascular Diseases

“…В проекте UK10K Consortium была показана ассоциация гипертриглицеридемии с редкими вариантами гена ADIPOQ, а учитывая связь гипертриглицеридемии с развитием атеросклероза, можно предполагать и влияние вариантов гена ADIPOQ на его развитие [8,9]. Также показана ассоциация ряда ВНП гена ADIPOQ с уровнем адипонектина [7,[10][11][12][13] и со степенью выраженности атеросклероза [14]. В то же время, имеются данные о различном влиянии одних и тех же ВНП в разных популяциях на уровень адипонектина в крови и развитие СД [7,12,[15][16][17].…”

“…Muiya N, et al установили корреляцию ряда ВНП 3'UTR области гена ADIPOQ с метаболическими факторами риска и сердечно-сосудистыми заболеваниями, тем самым показав важность этого локуса гена в патогенезе атеросклероза [14].…”