DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency

Abstract

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 +/- 1.9 vs 5.0 +/- 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.

Up-regulation of MSH2, XRCC1 and ATM genes in patients with type 2 diabetes and coronary artery disease

“…Patients with genotypes that decrease DNA repair efficacy are more susceptible to CAD [10]. Deficiency of the ataxiatelangiectasia mutated (ATM) protein that senses double strand breaks and X-ray repair cross-complementing 1 (XRCC1) that acts as the scaffold in the BER raise the risk of CAD [10,11]. The MutS protein homolog 2 (MSH2) is another protein of the repair system which its defect leads to MSI, a condition that was observed in atherosclerotic plaques frequently [12].…”

“…DNA strand breaks repair, base excision repair (BER) and mismatch repair (MMR) systems actively detect and repair DNA strand breaks and mutated nucleotides such as oxidized ones [7][8][9]. Patients with genotypes that decrease DNA repair efficacy are more susceptible to CAD [10]. Deficiency of the ataxiatelangiectasia mutated (ATM) protein that senses double strand breaks and X-ray repair cross-complementing 1 (XRCC1) that acts as the scaffold in the BER raise the risk of CAD [10,11].…”

DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

“…In patients with ESRD, DNA damage has been shown by numerous biomarkers, such as the analysis of sister chromatid exchange and chromosomal aberrations, 37 comet assay (single-cell gel electrophoresis) in peripheral lymphocytes, 21 8-hydroxy 2-deoxyguanosine content in leukocytes 38 and mitochondrial DNA deletions in skeletal muscle. Moreover, the XRCC1 399Gln gene variant has been associated with arthrosclerotic coronary artery disease, schizophrenia, pterygium, cataracts and systemic lupus erythematosus 3,[39][40][41] as well as various cancer types such as breast, lung, prostate, renal, carcinomas of head and neck, stomach, colon and acute lymphoblastic leukemia. [42][43][44][45][46][47][48][49] Combinations of common genetic polymorphisms may increase or decrease the susceptibility to certain diseases.…”

“…Genomic damage may also be involved in initiation as well as progression of cardiovascular diseases. 3 ESRD is associated with a high incidence of cancers and cardiovascular diseases. 4 Among the several pathogenic mechanisms suggested to explain these phenomena, there are uremia per se, micro inflammation and oxidative stress, 5 which involves the whole cell structure (proteins, membrane lipids, carbohydrates and DNA).…”

Molecular Studies on Coronary Artery Disease—A Review

“…CAD is a multifactorial process that appears to be due to the interaction of environmental risk factors with multiple predisposing genes [9]. Majority of patients who experience a CAD event have one or more of the conventional risk factors for atherosclerosis and so do many people who have not yet experienced such an event.…”