Tehran University Medical Journal

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Background: Pi-GST and Mu-GST are subclasses of glutathione S-transferase that present on human sperm surface and play an important role against oxidative stress. Therefore, any defects in the enzyme activity may be associated with male infertility.In this study the polymorphisms of GSTM1 and GSTP1 in association with enzyme activity and sperm parameters were studied.

Methods: This case-control study involved 95 men with oligoastenoteratozoospermia and 26 controls with normozoospermia. Semen analyses were carried out according to WHO guidelines. Blood DNA was extracted using salting out procedures. GSTM1 and GSTP1 polymorphisms gene were determined through PCR-RFLP and multiplex PCR, respectively. Finally, Glutathione S-transferase activity was measured.

Results: Frequencies of GSTM1 null genotype in oligoastenoteratospermic and normospermic groups were 52.1% and 53.8% respectively. There were no statistically significant differences in sperm parameters and enzyme activity between GSTM1 null and positive genotypes in two groups. There were no statistically significant differences in glutathione S-transferase activity between oligoastenoteratospermia and normospermic groups (p>0.05). All the 121 men in this study had Ile/Ile genotypes at 105 codon of GSTP1. Frequency of normal homozygote (114Ala/Ala), heterozygote (114Ala/Val) and mutant homozygote (114Val/Val) genotypes in oligoastenoteratospermic group were 81.1%, 17.9% and 1.1% respectively but in the control group they were 88.5%, 11.5% and null.

Conclusions: Total glutathione S-transferase activity and sperm parameters were not affected by deficient Glutathione S-transferase activity in GSTM1 null genotype. Compensate activity of other sperm surface glutathione S-transferase isozymes, like GSTP1, may justify the cause.

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Background: Uterine leiomyoma is one of the most common benign smooth muscle tumors occurring in 20-40% of women worldwide in their reproductive years. Recent studies revealed that estrogen plays an important role in the pathogenesis of this disease. Since glutathione S-transferase (GST) gene family are involved in the biosynthesis of estrogen, the prior probability that variants at this locus are associated with uterine leiomyoma is likely to be above the null. Therefore, this study was carried out to examine whether GSTP1 polymorphism (Ile105Val) is associated with increased risk of uterine leiomyoma in Iranian population. Methods: In this case-control study, 50 women diagnosed with uterine leiomyoma and 50 healthy controls were recruited from subjects referred to the Pasteur Institute of Iran from November 2012 to September 2013. The genomic DNA was extracted from peripheral blood leucocytes using the standard phenol-chloroform method and subsequently the GSTP1 polymorphism was genotyped using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Logistic regression analysis was applied to estimate odds ratios and 95% confidence intervals after age adjustment using the SPSS statistical software package, version 18.0. Results: The results showed significant differences between case and control groups in terms of genotype frequency (P<0.0001). In addition, the results indicated that the presence of the valine allele significantly increased risk of uterine leiomyoma about three times more in individuals carrying the mutant allele compared to control group (Odds Ratio: 3.34 95%CI: 1.82-6.15 P<0.0001). Conclusion: To our knowledge, this is the first study performed in Iranian population assessing the association between GSTP1 Ile105Val polymorphism and risk of uterine leiomyoma. However, further extensive studies with a large number of samples from different populations and ethnicities are required to validate the results obtained in this study.