Association Between Genetic Variants of DNA Repair Genes and Coronary Artery Disease

Abstract

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.

Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case–control study. The HUNT Study

“…individuals carrying the variant allele of XRCC1 rs25487 (Arg/Gln or Gln/Gln) [44]. Moreover, while we found no association between OGG1 rs1052133 variants and risk of MI, another study found an increased risk of acute coronary syndrome in carriers of the variant Cys allele [41]. However, the same study showed no association between OGG1 rs1052133 and chronic CAD, which complicates the interpretation of their results [41].…”

“…However, we believe that our findings could encourage others to include NEIL3 rs12645561 in their study populations. Notably, we could not find an association of OGG1 rs1052133 with MI, which has been associated with MI in other studies [41]. Thus, replication of SNP association studies is important to draw conclusions about a specific SNP -phenotype association.…”

“…Moreover, while we found no association between OGG1 rs1052133 variants and risk of MI, another study found an increased risk of acute coronary syndrome in carriers of the variant Cys allele [41]. However, the same study showed no association between OGG1 rs1052133 and chronic CAD, which complicates the interpretation of their results [41]. Difficulties in reproducing associations between SNPs affecting genes in the BER pathway and cardiovascular disease can at least partly reflect that several of the published studies are relatively small.…”

“…However, the results seem to be conflicting. For instance, four studies report no association between XRCC1 rs25487 polymorphism and CVD [39][40][41][42] while one study reported decreased risk of stroke in carriers of the variant rs25487 allele (Arg/Gln or Gln/Gln) [43]. In contrast, another study showed increased risk of coronary artery disease (CAD) in Table 3 Associations of DNA repair SNPs with risk of myocardial infarction (ORs (95% CI), [p-value]).…”

Association of the XPD and XRCC3 gene polymorphisms with oral squamous cell carcinoma in a Northeastern Brazilian population: A pilot study

“…On the other hand, one of the polymorphisms found in the XRCC3 gene is characterized by a non-conservative substitution of the amino acid Thr for Met in codon 241 (exon 7). This polymorphism has been studied regarding its influence on the sensitivity to radiation and induction of DNA damage (Gokkusu et al, 2013). The objective of this study was to evaluate the association between the frequency of the XPD-Lys751Gln (rs13181) and XRCC3-Thr241Met (rs861539) polymorphisms and the clinical-pathological profile of a series of OSCC cases.…”