Association of -۷۷T>C and Arg۱۹۴trp polymorphisms of XRCC۱ 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. ۵۰% of such cases occur in mitotic cells where single-strand breaks occur spontaneously or due to ionizing radiation. X-ray repair cross-complementing protein ۱ (XRCC۱) as a key element, participate in the base excision repair (BER) and Single-strand Break Repair (SSBR) pathways. It has been suggested that XRCC۱ functions as a scaffold protein able to coordinate and facilitate the various steps of DNA repair pathways. Two Single Nucleotide Polymorphisms (SNPs) (Arg۱۹۴Trp and -۷۷T>C) were reported to affect the function and expression of XRCC۱, respectively. Materials and Methods:A case-control study was performed to investigate the relation between these polymorphisms and the CAD development. A population of ۴۰۶ individuals was screened for SNPs by Restriction Fragment Length Polymorphisms (RFLP) method. Results: XRCC۱ Arg۱۹۴Trp polymorphism was associated with increased risk of CAD in examined population under a dominant model (Odds-ratio=۲.۶۰۴, P-value=۰.۰۰۱). Also the SNP of -۷۷T>C revealed a protective role in the population under a dominant model (Odds-ratio=۰.۶۱۸, P-value=۰.۰۳۲). 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.

Keywords:

Atherosclerosis , CAD , DNA damage , DNA repair , Single nucleotide poly-morphism , X-ray repair cross comple-menting protein