Amirhossein Ahmadi1, Mehrdad Behmanesh2, Mohammad Ali Boroumand3, Mahmoud Tavallaei4. 1. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran. 2. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran. Electronic address: behmanesh@modares.ac.ir. 3. Department of Pathology, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran. 4. Human Genetics Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran.
Abstract
AIMS: Coronary 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. METHODS: Expression 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. RESULTS: Significant 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. CONCLUSION: These results suggest that expression levels of DNA repair genes may serve as informative biomarkers for identifying patients with T2DM and CAD.
AIMS: Coronary 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. METHODS: Expression 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. RESULTS: Significant 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. CONCLUSION: These results suggest that expression levels of DNA repair genes may serve as informative biomarkers for identifying patients with T2DM and CAD.
Authors: Teresa Infante; Ernesto Forte; Concetta Schiano; Carlo Cavaliere; Carlo Tedeschi; Andrea Soricelli; Marco Salvatore; Claudio Napoli Journal: Am J Transl Res Date: 2017-07-15 Impact factor: 4.060