Genetic polymorphisms in DNA repair gene APE1, XRCC1 and XPD and the risk of pre-eclampsia

Abstract 

Objective

Oxidative stress has been postulated as a major contributor to placental hypoperfusion and ischemia in pre-eclampsia (PE). Reactive oxygen species (ROS) generated during placental ischemia can cause oxidative damage to nucleic acids. Base excision repair (BER) and nucleotide excision repair (NER) are major pathways responsible for removing the oxidative DNA damage. Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage.

Study design

In order to investigate the possible association between DNA repair genes and PE susceptibility, we analyzed genotype and allele distributions of APE1-148, XRCC1-194, XRCC1-399 and XPD-751 genes in 101 patients with PE and 107 healthy women. Differences in genotype distributions and allele frequencies in the cases and the controls were compared for statistical significance using the χ²-test. Haplotype frequencies were estimated using a contingency χ²-test. One-way ANOVA and Mann–Whitney U-test were used for the statistics of the clinical and biochemical parameters.

Results

No significant association between PE and the variant alleles of APE1 codon 148 (OR: 0.77, 95% CI=0.51–1.15), XRCC1 codon 194 (OR: 0.64, 95% CI=0.30–1.37), XRCC1 codon 399 (OR: 1.16, 95% CI=0.78–1.74) and XPD codon 751 (OR: 1.21, 95% CI=0.81–1.80) was observed. Results of our haplotype analysis demonstrated that there is a high linkage disequilibrium (D′: 1.0, r²=0.042) between the haplotypes of XRCC1 codon 194 and codon 399 markers.

Conclusions

These preliminary results suggest that the polymorphic variants of APE1-148, XRCC1-194, XRCC1-399, and XPD-751 genes are not significant risk factors for PE development.

Keywords: Preeclampsia, Polymorphism, DNA repair, APE1, XRCC1, XPD