title: Up-regulation of MSH2, XRCC1 and ATM genes in patients with type 2 diabetes and coronary artery disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results suggest that expression levels of DNA repair genes may serve as informative biomarkers for identifying patients with T2DM and CAD.
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Ahmadi
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran. Electronic address: behmanesh@modares.ac.ir.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Behmanesh
authors.affiliation: Department of Pathology, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Boroumand
authors.affiliation: Human Genetics Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Tavallaei
mesh_terms: D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015854:Up-Regulation / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
keywords: Atherosclerosis; Biomarker; Coronary artery disease; DNA damage