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Infrequent TRIB3 coding variants and coronary artery disease in type 2 diabetes.

ABSTRACT: OBJECTIVE:Genes that modulate insulin sensitivity may also be involved in shaping the risk of coronary artery disease (CAD). The relatively common TRIB3 Q84R polymorphism (rs2295490) has been associated with abnormal insulin signaling, endothelial dysfunction, insulin resistance, and pro-atherogenic phenotypes. The aim of our study was to investigate the association between low-frequency TRIB3 coding variants and CAD in patients with type 2 diabetes (T2D). METHODS:Three case-control studies for CAD from Italy and US were analyzed, for a total of 1565 individuals, all with type 2 diabetes. Infrequent variants were identified by re-sequencing TRIB3 exons in 140 "extreme cases" and 140 "super-controls" and then genotyped in all study subjects. RESULTS:TRIB3 infrequent variants (n = 8), considered according to a collapsing rare variants framework, were significantly associated with CAD in diabetic patients from Italy (n = 700, OR = 0.43, 95% CI 0.20-0.91; p = 0.027), but not from the US (n = 865, OR = 1.22, 95% CI 0.69-2.18; p = 0.49). In the Italian sets, the association was especially strong among individuals who also carried the common R84 variant. CONCLUSION:Although preliminary, our finding suggests a role of TRIB3 low-frequency variants on CAD among Italian patients with T2D. Further studies are needed to address the role of TRIB3 infrequent variants in other populations of both European and non-European ancestries.

SUBMITTER: Prudente S

PROVIDER: S-EPMC4872508 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Infrequent TRIB3 coding variants and coronary artery disease in type 2 diabetes.

Prudente Sabrina S Bailetti Diego D Mendonca Christine C Mannino Gaia Chiara GC Fontana Andrea A Andreozzi Francesco F Hastings Timothy T Mercuri Luana L Alberico Federica F Basile Giorgio G Copetti Massimiliano M Sesti Giorgio G Doria Alessandro A Trischitta Vincenzo V

Atherosclerosis 20150717 1

<h4>Objective</h4>Genes that modulate insulin sensitivity may also be involved in shaping the risk of coronary artery disease (CAD). The relatively common TRIB3 Q84R polymorphism (rs2295490) has been associated with abnormal insulin signaling, endothelial dysfunction, insulin resistance, and pro-atherogenic phenotypes. The aim of our study was to investigate the association between low-frequency TRIB3 coding variants and CAD in patients with type 2 diabetes (T2D).<h4>Methods</h4>Three case-contr ...[more]

PMID: 26253791

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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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Infrequent TRIB3 coding variants and coronary artery disease in type 2 diabetes.

Publications

Infrequent TRIB3 coding variants and coronary artery disease in type 2 diabetes.

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