Association between susceptibility to advanced pelvic organ prolapse and glutathione S-transferase P1 Ile105Val polymorphism

Abstract

Objective: Oxidative stress is associated with the pathogenesis of pelvic organ prolapse (POP). Because glutathione S-transferases (GSTs) are the major detoxification enzymes which protect cells against oxidative stress, genetic variations in the GST gene may modulate the risk of POP. This study aimed to determine the association between advanced POP and the polymorphisms of GSTM1, GSTT1 and GSTP1 (rs1695).

Study design: This is a hospital-based case-control study. The POP group consisted of 189 women diagnosed with POP stage III or IV, and the control group consisted of 156 postmenopausal women with POP stage 0 or I. The GSTM1 and GSTT1 null mutations were detected by multiplex PCR, and the GSTP1 Ile105Val polymorphism was genotyped by real-time PCR analysis using a TaqMan assay.

Results: There was no significant association between the GSTM1 and GSTT1 null mutations and advanced POP (p>0.05). The distribution of the GSTP1 Ile105Val genotypes, however, was significantly different between the POP and control groups (AA/AG/GG rates=74.1%/25.9%/0% vs. 64.1%/32.1%/3.8%, p=0.008), and the G allele frequency was significantly lower in the POP group than in the control group (13.0% vs. 19.9%, p=0.014). Women with the non-AA genotype had a 0.63-fold lower risk of developing advanced POP than women with the AA genotype (95% CI, 0.39-0.99), and women with the G allele had a 0.60-fold lower risk of advanced POP than women with the A allele (95% CI, 0.40-0.90).

Conclusions: The GSTP1 Ile105Val polymorphism is a protective factor against advanced POP.

Keywords: Glutathione S-transferase; Oxidative stress; Pelvic organ prolapse.