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.

The study was designed to investigate the associations of polymorphisms Ile462Val and 3801T>C of the cytochrome P450 1A1 (CYP1A1) gene with idiopathic male infertility (IMI) and to assess the impact of smoking status on the relationship between the polymorphisms and the susceptibility to the disease. DNA samples from 203 patients with IMI and 227 fertile men were genotyped for the polymorphisms by a polymerase chain reaction and restriction fragment length polymorphism methods. We found for the first time that the increased risk of IMI in carriers of genotype 462Ile/Val of the CYP1A1 gene occurred only in smoker men (odds ratio [OR] = 1.91; 95% confidence interval [CI] 1.01-3.59), whereas nonsmoker men did not have the risk of infertility (OR = 1.58; 95% CI 0.66-3.76). The results of our study demonstrate that the analysis of gene-environment interactions is necessary to explain conflicting results of genetic studies of IMI and to improve our understanding of the mechanisms of the disease.

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