Gokkusu Cahide, Cakmakoglu Bedia, Dasdemir Selcuk, Tulubas Feti, Elitok Ali, Tamer Sule, Seckin Sule, Umman Berrin
Department of Biochemistry, Istanbul University, Istanbul, Turkey.
Genet Test Mol Biomarkers. 2013 Apr;17(4):307-13. doi: 10.1089/gtmb.2012.0383. Epub 2013 Jan 31.
Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of atherosclerosis. Genetic research on coronary artery disease (CAD) has traditionally focused on investigation aimed at identifying disease-susceptibility genes. The aim of this study was to investigate the relationship between AP-endonuclease-1 (Asp148Glu), XRCC1 (Arg399Gln), XRCC3 (Thr241Met), XPD (Lys751Gln), XPG (Asp1104His), and hOGG1 (Ser326Cys), gene polymorphisms and the risk of developing CAD in a Turkish population. The study population consisted of 197 patients with acute coronary syndrome (ACS) with chronic CAD and 135 healthy subjects' age and sex matched. Gene polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism method. We demonstrated for the first time, a positive association of XRCC3 and hOGG1 DNA repair gene variants with CAD risk. XRCC3 Thr/Thr genotype and Thr allele frequencies were significantly increased in ACS and chronic CAD patients compared with the control group (p<0.05). It was also observed that there is a protective role of XRCC3 Met alleles against both ACS and chronic CAD (p<0.05). hOGG1 Cys alleles were found significantly higher in ACS patients than in the control group and carriers of the Cys allele had a 1.7-fold increased risk for ACS. In addition, we confirmed the association of XRCC3 Thr241Met and hOGG1 Ser326Cys gene variants with CAD by haplotype analysis. We found that CAD risk is associated with XRCC3 Thr: hOGG1 Cys haplotype, whereas XRCC3 Met: hOGG1 Ser haplotype was found to be protective against the disease. The preliminary results suggested that XRCC3 and hOGG1 genetic variants may be risk factors by affecting the enzyme's function that may lead to development of CAD.
DNA修复基因的多态性可能与DNA损伤修复效率的差异相关，并可能影响个体患动脉粥样硬化的风险。传统上，关于冠状动脉疾病（CAD）的基因研究主要集中在旨在识别疾病易感基因的调查上。本研究的目的是调查AP核酸内切酶-1（Asp148Glu）、XRCC1（Arg399Gln）、XRCC3（Thr241Met）、XPD（Lys751Gln）、XPG（Asp1104His）和hOGG1（Ser326Cys）基因多态性与土耳其人群患CAD风险之间的关系。研究人群包括197例患有慢性CAD的急性冠状动脉综合征（ACS）患者和135名年龄和性别匹配的健康受试者。通过聚合酶链反应-限制性片段长度多态性方法确定基因多态性。我们首次证明，XRCC3和hOGG1 DNA修复基因变异与CAD风险呈正相关。与对照组相比，ACS和慢性CAD患者中XRCC3 Thr/Thr基因型和Thr等位基因频率显著增加（p<0.05）。还观察到XRCC3 Met等位基因对ACS和慢性CAD均具有保护作用（p<0.05）。发现ACS患者中hOGG1 Cys等位基因显著高于对照组，Cys等位基因携带者患ACS的风险增加1.7倍。此外，我们通过单倍型分析证实了XRCC3 Thr241Met和hOGG1 Ser326Cys基因变异与CAD的关联。我们发现CAD风险与XRCC3 Thr:hOGG1 Cys单倍型相关，而XRCC3 Met:hOGG1 Ser单倍型对该疾病具有保护作用。初步结果表明，XRCC3和hOGG1基因变异可能通过影响酶的功能而成为导致CAD发生的风险因素。
