The association of glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) with idiopathic male infertility.

The effects of the GST genes (GSTM1, GSTT1 and GSTP1) on male factor infertility have not been well elucidated. A case-control study was performed to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 166 men suffering from idiopathic oligoasthenoteratozoospermia (OAT) and an equal number of age-matched healthy fertile male controls. Genomic DNA extracted from the peripheral blood, was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Multivariate regression analysis showed an increase in risk to infertility in the patients with null genotype of GSTM1 (OR: 2.18; 95% CI: 1.64-3.32; P=0.001) or GSTT1 (OR: 1.88; 95% CI:1.12-2.52; P=0.04). Our data further showed that combination of deletion genotypes of GST (GSTM1 and GSTT1) pose an even higher risk of infertility. In addition, GSTP1 wild-type genotype in combination with GSTM1 null or GSTT1 null genotype increased probability for infertility (OR: 2.47, 95% CI: 1.46-4.17: and OR: 2.69, 95% CI: 1.39-5.32, respectively). Similarly a much higher risk for infertility was noted in the patients carrying a genotype combination of GSTM1 null, GSTT1 null and GSTP1 (Ile/Ile) (OR: 4.45; 95% CI: 1.59-12.24; P=0.002). The variant genotypes of GSTP1 (Ile/Val and Val/Val) resulted in a significant decreased risk to infertility in the cases (OR: 0.44; 95% CI: 0.29-0.78, P=0.004). These results support the hypothesis of increased risk of GSTM1 or GSTT1null genotypes for developing infertility, but the nondeletion GSTM1 and GSTT1genotypes emerged as protective factors.