Association of premature ovarian failure with the polymorphisms of DNA repair genes XPD and XRCC1

Premature ovarian failure (POF) is a heterogeneous disorder defined as the cessation of ovarian function accompained by elevated gonadotrophins and low estrogen level before the age of 40 which affects approximately 1% of women of reproductive age. In 90% of the cases of POF, the etiology remains unknown. Fewer than 500 of a women?s original seven million oocytes are released in their entire reproductive life span. POF may result from either a decreased number of follicles being found during ovarian development or an increased rate of follicle loss. Epidemiological studies have demonstrated that exposure to certain DNA damaging agents may result in decreased fertility and reductions in ovarian follicle numbers. The polymorphisms of DNA repair genes may alter the functions of DNA repair enzymes and unrepaired DNA damage can activate apoptosis. We therefore investigated whether polymorphisms in the XPD and the XRCC1 genes associated with idiopathic POF in Turkish population. For this, we analyzed the frequency of XPD-Lys751Gln, XRCC1-Arg194Trp and XRCC1-Arg399Gln polymorphisms in patients with POF and the controls. The patient group with 25 POF subjects between 17 and 39 years old was chosen for this study. The control group included 25 women ranging from 21 to 64 years old who underwent menopause after age 40 or who had regular menstrual cycles. DNA was isolated from peripheral blood leukocytes by standard methods. Detection of polymorphisms was done by rapid capillaryPCR with melting curve analysis using fluorescence-labeled hybridization probes in a LightCycler. In this study, no statistically significant differences were found in genotype distributions or allel frequencies of the evaluated polymorphisms between the patients with POF and the controls. For XPD-Lys751Gln polymorphism, POF group showed a significantly lower frequency of Gln/Gln+Lys/Gln genotype compared with the controls. We found that there is a protective role of 751Gln allel against POF.