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Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis.

ABSTRACT: Single-nucleotide polymorphisms predisposing to coronary artery disease (CAD) have been shown to predict cardiovascular risk in healthy individuals when combined into a genetic risk score (GRS). We examined whether the cumulative burden of known genetic risk variants associated with risk of CAD influences the development and progression of coronary atherosclerosis.We investigated the combined effects of all known CAD variants in a cross-sectional study of 8622 Icelandic patients with angiographically significant CAD (? 50% diameter stenosis). We constructed a GRS based on 50 CAD variants and tested for association with the number of diseased coronary arteries on angiography. In models adjusted for traditional cardiovascular risk factors, the GRS associated significantly with CAD extent (difference per SD increase in GRS, 0.076; P=7.3 × 10(-17)). When compared with the bottom GRS quintile, patients in the top GRS quintile were roughly 1.67× more likely to have multivessel disease (odds ratio, 1.67; 95% confidence interval, 1.45-1.94). The GRS significantly improved prediction of multivessel disease over traditional cardiovascular risk factors (?(2) likelihood ratio 48.1; P<0.0001) and modestly improved discrimination, as estimated by the C-statistic (without GRS versus with GRS, 64.0% versus 64.8%) and the integrated discrimination improvement (0.52%). Furthermore, the GRS associated with an earlier age at diagnosis of angiographic CAD. These findings were replicated in an independent sample from the Emory Biobank study (n=1853).When combined into a single GRS, known genetic risk variants for CAD contribute significantly to the extent of coronary atherosclerosis in patients with significant angiographic disease.

SUBMITTER: Bjornsson E

PROVIDER: S-EPMC5903266 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis.

Bjornsson Eythor E Gudbjartsson Daniel F DF Helgadottir Anna A Gudnason Thorarinn T Gudbjartsson Tomas T Eyjolfsson Kristjan K Patel Riyaz S RS Ghasemzadeh Nima N Thorleifsson Gudmar G Quyyumi Arshed A AA Thorsteinsdottir Unnur U Thorgeirsson Gudmundur G Stefansson Kari K

Arteriosclerosis, thrombosis, and vascular biology 20150416 6

<h4>Objective</h4>Single-nucleotide polymorphisms predisposing to coronary artery disease (CAD) have been shown to predict cardiovascular risk in healthy individuals when combined into a genetic risk score (GRS). We examined whether the cumulative burden of known genetic risk variants associated with risk of CAD influences the development and progression of coronary atherosclerosis.<h4>Approach and results</h4>We investigated the combined effects of all known CAD variants in a cross-sectional st ...[more]

PMID: 25882067

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Project description:BackgroundAdiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common single nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with the risk of coronary artery disease (CAD) and its angiographical severity in type 2 diabetes in Chinese population.Methods11 tagging SNPs were genotyped in 1110 subjects with or without CAD in type 2 diabetes. Variants of adiponectin gene were determined by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by sandwich enzyme-linked immunosorbent assay. The severity and extent of coronary atherosclerosis were assessed using the angiographic Gensini score and Sullivan Extent score.ResultsAmong the 11 SNPs, the minor G allele of SNP rs266729 was significantly associated with higher odds of CAD (odds ratio (95% CI) = 1.49 (1.10 - 2.16), P = 0.022) after adjusting for covariates. In stepwise multivariate logistic regression, SNP rs266729 was a significant independent factor of CAD. Multivariate linear regression analysis revealed that rs266729 (β = -0.101, P < 0.0001), rs182052 (β = -0.044, P = 0.0035), and rs1501299 (β = 0.073, P < 0.0001) were significantly associated with adiponectin level, and also indicated that the minor G allele of SNP rs266729 had higher Gensini score (β = 0.139, P < 0.001) and Sullivan Extent score (β = 0.107, P < 0.001). Haplotypes analysis revealed different haplotype distributions in case and control subjects (P = 0.0003), with two common haplotypes GGG and GAG of the rs266729, rs182052, and rs1501299 being associated in heterozygotes with a greater than threefold increase in cardiovascular risk (odds ratio (95% CI)=3.39 (1.83 - 6.30), P = 0.0001).ConclusionsIn our population, genetic variants in the adiponectin gene influence plasma adiponectin levels, and one of them is a strong determinant of CAD susceptibility and its angiographical severity in type 2 diabetes. This study has provided further evidence for a role of adiponectin in the development of CAD.

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Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis.

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Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis.

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