Joint effect of glutathione S-transferase genotypes and cigarette smoking on idiopathic male infertility

Abstract

Inconsistent results of association studies investigated the role of glutathione S-transferase genes in idiopathic male infertility may be explained by ethnical differences in gene-gene and gene-environm ent interactions. In this study, we investigated a joint contribution of GSTM1, GSTT1 and GSTP1 gene polym or phisms and cigarette smoking to the risk of idiopathic infertility in Russian men. DNA samples from 203 infertile and 227 fertile m en were genotyped by a multiplex polymerase chain reaction (GSTM1 and GSTT1 deletions) and PCRrestriction fragment length polym orphism (GSTP1 I105V) methods. The GSTP1 genotype 105IV was associated with increased risk of male infertility (OR = 1.50 95% Cl 1.02-2.20 P = 0.04). Genotype com binations GSTP1 10511/ GSTT1 del (Gl), GSTM1 delIGSTT1 del (G2) and GSTM1 + IGSTT1 del (G3) were associated with decreased risk of male infertility (P < 0.003), whereas a genotype com bination GSTP1 1051V/GSTT1 + (G4) was associated with increased disease risk (P = 0.001). The genotype com binations G3 and G4 showed a significant association with infertility in smokers; however, nonsm ok ers carriers did show the disease risk. In conclusion, GSTM1, GSTT1 and GSTP1 genes are collectively involved in the development of idiopathic male infertility and their phenotypic effects on the disease risk are potentiated by cigarette smoking.

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk

“…These findings contradict the results of the recent meta-analysis that we discussed above. [42] Indeed, among the nine case-control studies in the current meta-analysis, five studies[2627293233] showed no association between the Ile105Val polymorphism and male infertility, and three[212830] reported an increased risk, whereas only one study[31] suggested a decrease risk. The present study revealed obvious between-study heterogeneity in several genetic models.…”

“…Moreover, many recent studies have been published concerning the association between the GSTP1 Ile105Val polymorphism and male infertility risk. [2126272829303233]…”

“…Yarosh et al . [30] observed that the genotype combination GSTP1 105Ile/Ile and GSTT1 null was associated with decreased risk of male infertility, whereas the genotype combination GSTP1 105 Ile/Val and GSTT1 was associated with increased risk. However, we could not further evaluate the gene-gene and gene-environment interactions or carry out a haplotype analysis of the development of male infertility because the original data for the eligible studies could not be obtained.…”

“…To date, several case-control studies have investigated the association between the GSTP1 Ile105Val polymorphism and risk of male infertility,[212627282930313233] but the results have been inconclusive owing to the limitation of individual studies, for example, relatively small sample size and/or differences in patient populations, ethnicity, or genotyping methods. Therefore, we carried out a systematic review and meta-analysis of all available data to better assess the overall effects of this polymorphism on male infertility risk.…”

NRF2 gene expression and DNA fragmentation markers as possible predictors of chronic smoking induced spermatozoa dysfunction in infertility with normal seminogram

“…It is worth to say that smoking could work on the susceptible patient having NRF2 single nucleotide polymorphism [21] . It is expected that genetic variations in major antioxidant genes will alter the susceptibility of a male to infertility and defective spermatogenesis [22] . Directly, smoking can also affect NRF2 proteins and impair antioxidant induction [23] .…”