A study of polymorphisms in XRCC1, APE1 and XPD DNA repair genes in polycystic ovary syndrome patients

Polycystic ovary syndrome (PCOS) is a reproductive endocrinopathy characterised by chronic anovulation, oligomenorrhea, and hyperandrogenism. PCOS is reported to arise from the interaction of genetic and environmental factors. Further studies report that PCOS patients have DNA damage and chromosome breakage. Such studies bring to mind the genes that are involved in DNA repairing. At present, several DNA repair genes and, as products of these genes, certain polymorphisms that alter the activity of proteins are known in the literature. The aim of this dissertation is to study the genomic instability that have been reported in PCOS cases along with the relationship between XRCC1 Arg194Trp, XRCC1 Arg399Gln, APE1 Asp148Glu, and XPD Lys751Gln polymorphisms in order to contribute to the pathogenesis of PCOS. The study has started by isolating genomic DNA samples obtained from the blood samples in EDTA tubes from the patients in the study group. Using the real-time polymerase chain reaction, the genotypes of these patients were determined in terms of four polymorphisms of three different genotypes (XRCC1 Arg194Trp, XRCC1 Arg399Gln, APE1 Asp148Glu, and XPD Lys751Gln). Comparing the control groups at the end of the study, the results have not shown any statistically significant difference as far as XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XPD Lys751Gln polymorphisms are concerned. However, there were notable differences between the groups in terms of APE1 Asp148Glu polymorphism. Associated with this condition, it has been noted that both mutant allele (Glu) frequency (37,72% in the study group; 19,23% in the control group) and homozygous mutant genotype (Glu/Glu) frequency (with 12.28%) have been higher in the study group. Evaluating the clinical features of PCOS in conjunction with polymorphism results, it has also been observed that the only remarkable difference between the genotypes was related to body mass index (BMI) and to APE1 Asp148Glu. Furthermore, it has been found out that BMI tends to be lower in patients with Asp/Asp genotypes (22,85) compared to patients with heterozygous (26,24) and homozygous mutant (25,81) genotypes. Keywords: XRCC1, APE1, XPD, Polycystic Ovary Syndrome