Association of Polymorphisms (rs 1799782, rs25489 and rs25487) in XRCC1 and (rs 13181) XPD genes with Acute Coronary Artery Syndrome in Subjects from Multan, Pakistan

Acute coronary artery syndrome (ACS) is the major cause of mortality in Pakistan with genetic and environmental influence on the incidence of the disease. This case-control study was designed to find out if a correlation is existing between ACS and single nucleotide polymorphisms (SNPs) in DNA repair genes XPD [at codon 751, rs 13181 (Lys to Gln)] and XRCC1 [at codon 399, rs25487 (Arg to Gln); 280, rs25489 (Arg to His) and 194, rs 1799782 (Arg to Trp)] either individually or in various combination with each other (haplotype analysis). The objective of this study was to find out the association of various studied risk factors and serum lipid profile of the subjects with the disease, if any. PCR-RFLP method was used to determine genotype at specific codon in 221 subjects (115 ACS patients and 106 healthy controls) from Southern Punjab population. Genotypic and allelic frequency distribution among the cases and controls revealed that all the studied SNPs were not individually associated with the ACS. Haplotype analysis revealed that subjects having wild type combination of all three XRCC1 SNPs had greater susceptibility to ACS than any other studied genotypic combinations. Analysis of risk factors revealed that hypertension (P<0.001), age (P=0.05), education (P<0.001), gender (P<0.001), family history (P=0.005), smoking habit (P=0.002) and diabetes (P<0.001) were significantly associated with the incidence of ACS. Serum lipid profile analysis indicated that cholesterol level was significantly higher (P=0.048) in patients (161.5mg/dL) than controls (142.1mg/dL) while triglyceride remained unaffected (P=0.87) when compared between the two treatments.