Poly(ADP-ribose) polymerase-1 gene polymorphism as a determinant of individual susceptibility to pelvic organ prolapse

Abstract

Introduction: Apoptotic cell death, likely induced by oxidative stress, contributes to the development of pelvic organ prolapse (POP). Because poly(ADP-ribose) polymerase-1 (PARP-1) is an important mediator of the cellular response to oxidative stress, genetic variations in the PARP-1 gene may play a role in the pathogenesis of POP. This study aimed to determine the association between POP and the Val762Ala polymorphism in the PARP-1 gene.

Methods: A total of 370 women were enrolled in the study. The patient group consisted of 215 women diagnosed with POP stage II or greater, whereas the control group consisted of 155 postmenopausal women with POP stage 0 or I who visited the hospital for treatment of benign gynecologic disease or a routine gynecologic checkup. Genomic DNA was extracted from peripheral blood samples with a DNA purification kit, and the PARP-1 Val762Ala polymorphism was genotyped by real-time PCR analysis using a TaqMan assay.

Results: The genotype distribution in the patient group was significantly different from that of the control group (TT/TC/CC rates were 33.5%/51.6%/14.9% and 29.0%/45.8%/25.2% for the POP and control groups, respectively

p=0.046). Furthermore, the C allele frequency was significantly lower in the patient group than in the controls (40.7% vs. 48.1%

p=0.046). Women with the CC genotype had a 0.513-fold lower risk of developing POP (95% confidence interval [CI], 0.282-0.934

p=0.029) than women with the TT genotype, and women with the C allele had a 0.742-fold lower risk of developing POP than women with the T allele (95% CI, 0.553-0.997

p=0.047). Moreover, when the data were re-analyzed excluding the women with mild POP (POP stage II), these observations were more prominent.

Conclusions: These findings suggest that the PARP-1 Val762Ala polymorphism reduces the risk of POP.