title: Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality.
abstract: 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 of toxicants on semen quality parameters has rarely been evaluated. In this analysis, we evaluated functional SNPs of three genes of the glutathione-S-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 GSTT1-1 and GSTM1-1 null genotypes and the GSTZ1 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 GSTM1 and GSTZ genotypes and increased occurrence of adverse sperm outcomes. However, the GSTT1 non-null genotype yielded the coefficients with the largest magnitude for sperm count and sperm concentration (beta=-0.528, 95% CI -1.238 to 0.199 and beta=-0.353, 95% CI -0.708 to 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.
authors.affiliation: Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC 27599, USA. andy_olshan@unc.edu
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Luben
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hanley
authors.forename: Sally D
authors.initials: SD
authors.lastname: Perreault
authors.forename: Ronna L
authors.initials: RL
authors.lastname: Chan
authors.forename: Amy H
authors.initials: AH
authors.lastname: Herring
authors.forename: Patricia V
authors.initials: PV
authors.lastname: Basta
authors.forename: David M
authors.initials: DM
authors.lastname: DeMarini
mesh_terms: D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013076:Sperm Count; D013094:Spermatozoa / Q000166:cytology*
chemical_list: D005982:Glutathione Transferase; C407705:GSTZ1 protein, human; C413545:glutathione S-transferase T1