Article ID Journal Published Year Pages File Type
2796226 Diabetes Research and Clinical Practice 2015 7 Pages PDF
Abstract

•Up-regulation of MSH2, XRCC1 and ATM genes was observed in T2DM patients with CAD.•ATM expression was correlated with CAD severity.•Single nucleotide polymorphisms in their promoters did not affect mRNA expression.•DNA repair genes expression may serve as useful biomarkers.

AimsCoronary artery disease (CAD) is a major problem in some patients with type 2 diabetes mellitus (T2DM). CAD has been suggested to be the main result of reduced efficacy of DNA repair systems. Analysis of the DNA repair system in patients with diabetes can potentially uncover the molecular basis of their susceptibility to the CAD. The aim of the present study was to compare the expression levels of some important DNA repair genes, including ATM, XRCC1 and MSH2, in CAD+ versus CAD− patients with T2DM. Furthermore, the relevance of putative single nucleotide polymorphisms (SNPs) in the promoter regions of these genes with mRNA expression was evaluated.MethodsExpression analysis was performed by RT-qPCR on 76 patients with T2DM (41 CAD+ and 35 CAD− individuals confirmed by angiography). The genotypes of the patients were examined by polymerase chain reaction-restriction fragment length polymorphism analysis.ResultsSignificant up-regulation of the MSH2 (2.49-fold, P = 0.001), XRCC1 (2.11-fold, P = 0.001) and ATM (2.15-fold, P = 0.003) genes was observed in patients with T2DM and CAD. We could not detect any function for SNPs by comparing gene expression. In a receiver operating characteristic (ROC) curve analysis, the area under the ROC curve for sum of relative expressions of all genes reached 0.81 (95% CI: 0.690–0.936, P = 0.003), which indicates a potential biomarker for identifying patients with T2DM and CAD.ConclusionThese results suggest that expression levels of DNA repair genes may serve as informative biomarkers for identifying patients with T2DM and CAD.

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Life Sciences Biochemistry, Genetics and Molecular Biology Endocrinology
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