RRM1, RRM2 and ERCC2 Gene Polymorphisms in Coronary Artery Disease

Altinkilic E. M., Isbir S., GÖRMÜŞ U., Yilmaz S. G., Dalan A. B., Duman S., ...Daha Fazla

IN VIVO, cilt.30, sa.5, ss.611-615, 2016 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 5
  • Basım Tarihi: 2016
  • Dergi Adı: IN VIVO
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.611-615
  • Marmara Üniversitesi Adresli: Evet

Özet

Background/Aim: Coronary artery disease (CAD) is a chronic inflammatory disease seen as formation of atherosclerotic plaques (atheroma) in coronary arteries. Recent published papers show that DNA damage and repair mechanisms play a crucial role on the development and severity of atheromas. In this study, we investigated nucleotide excision repair (NER) pathway-related gene polymorphisms in atherosclerosis. XPD, encoded by ERCC2 gene, is an ATP-depended helicase enzyme involved in the NER pathway. Ribonucleotide reductase (RR) is a tetrameric enzyme, synthesizing deoxyribonucleotides from ribonucleotides for DNA synthesis. RR is encoded by the RRM1 and RRM2 genes, which are two subunits of RR enzyme. Materials and Methods: DNA samples isolated from peripheral blood were genotyped with real-time polymerase chain reaction (RT-PCR) for RRM1 (rs12806698), RRM2(rs6859180) and ERCC2 (rs13181) genes. Results: The frequency of the RRM1 AC heterozygote genotype was found to be significantly lower (odds ratio (OR) = 0.369, 95% confidence interval (CI) = 0.179-0.760; p = 0.006), whereas the CC homozygote genotype was found to be significantly higher in patients compared to controls (OR = 7.636, 95% CI = 2.747-21.229; p = 0.000). In addition, the RRM1 A allele was higher in control group (p = 0.000, OR = 0.131 95% CI = 0.047-0.364). For the ERCC2 gene, GG genotype was significantly higher in control group (p = 0.017, OR = 0.387, 95%CI = 0.175-0.152) and TT genotype (p = 0.021) was higher in CAD group. TT genotype had a similar to 3-fold increased risk (OR = 3.615, 95%CI = 1.148-11.380) for CAD. Carrying T allele appears to be a risk factor for CAD (p = 0.017, OR = 2.586, 95%CI = 1.173-5.699), while the G allele might be a risk-reducing factor (p = 0.021, OR = 0.277, 95%CI = 0.088-0.871) for CAD. Conclusion: RRM1 and ERCC gene polymorphisms, having homozygous mutant genotype, might be a risk factor for CAD. RRM1 and ERCC wild type alleles are risk-reducing factor for CAD. Also, carrying RRM1 A allele might have a protective effect for smokers.