Association of -77T>C and Arg194trp polymorphisms of XRCC1 with risk of coronary artery diseases in Iranian population

Objective(s): Coronary artery disease (CAD) is the leading cause of death in both male and female worldwide. The main cause of CAD is the atherosclerosis of coronary arteries, which is, mostly caused by genetic alteration. 50% of such cases occur in mitotic cells where single-strand breaks occur spontaneously or due to ionizing radiation. X-ray repair cross-complementing protein 1 (XRCC1) as a key element, participate in the base excision repair (BER) and Single-strand Break Repair (SSBR) pathways. It has been suggested that XRCC1 functions as a scaffold protein able to coordinate and facilitate the various steps of DNA repair pathways. Two Single Nucleotide Polymorphisms (SNPs) (Arg194Trp and -77T>C) were reported to affect the function and expression of XRCC1, respectively. Materials and Methods:A case-control study was performed to investigate the relation between these polymorphisms and the CAD development. A population of 406 individuals was screened for SNPs by Restriction Fragment Length Polymorphisms (RFLP) method. Results: XRCC1 Arg194Trp polymorphism was associated with increased risk of CAD in examined population under a dominant model (Odds-ratio=2.604, P-value=0.001). Also the SNP of -77T>C revealed a protective role in the population under a dominant model (Odds-ratio=0.618, P-value=0.032). Conclusion:Our findings demonstrated a contributory role of these two SNPs in CAD. Furthermore, our results support the role of DNA damages and the malfunctions of DNA repair system in cardiovascular disease development in Iranian patients.