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Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality
Citation:
Olshan, A. F., T. J. Luben, N. M. HANLEY, S. D. PERREAULT, R. L. Chan, A. H. Herring, P. V. Basta, AND D. M. DEMARINI. Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality. MUTATION RESEARCH. Elsevier Science Ltd, New York, NY, 688(1-2):41-46, (2010).
Impact/Purpose:
We initiated this study to examine the influence of polymorphisms of genes that are either known or suspected to be involved in the metabolism of drinking water disinfection by-products. In particular, we examined polymorphisms of GSTM1, GSTT1, and GSTZ1. The GSTTI enzyme is known to metabolize the brominated trihalomethanes to mutagens, whereas the GSTZ1 enzyme metabolizes haloacids, such as dichloromethane. Understanding the influence of polymorphisms of these genes on sperm quality is a prerequisite for studies on the possible role of disinfection by-products on semen quality.
Description:
Background: Environmental, lifestyle, and occupational exposures on semen quality have been investigated in epidemiological studies with inconsistent results. Genetic factors involved in toxicant activation and detoxification have been examined in relation to the risk of outcomes such as cancer, cardiovascular, and neurologic disorders. However, the effect of common genetic variants in the metabolism oftoxicants on semen quality parameters has rarely been evaluated. In this analysis, we evaluated functional SNPs of three genes of the glutathioneS- transferase (GSTM1, GSTT1, GSTZ1) enzyme family. Methods: Participants were 228 presumed fertile men recruited as part of a community-based study. Semen outcome data from this study included total sperm count and concentration, sperm morphology, and sperm DNA integrity and chromatin maturity. DNA was obtained from 162 men from a mouth-rinse sample and genotyped for the presence of GSTT1-l and GSTM1-l null genotypes and the GSTZl SNPs at positions 94 (rs3177427) and 124 (rs3177429). We used multivariable linear regression to assess the relationship between each genotype and sperm outcomes. Results: Overall, our results did not reveal a consistent pattern between GSTMl and GSTZ genotypes and increased occurrence of adverse sperm outcomes. However, the GSTTl non-null genotype yielded the coefficients with the largest magnitude for sperm count and sperm concentration (~=-0.528, 95% CI.-1.238-0.199 and ~=-0.353, 95% CI -0.708-0.001, respectively), suggesting that it might be adverse. Conclusions: These results indicate that common polymorphisms in GST genes do not negatively impact sperm parameters in healthy men with good semen quality. Contrary to expectations, the GSTT1 non-null genotype was associated with reduced sperm concentration and count in semen. Further study with a larger study size and inclusion of gene-exposure interactions is warranted.
