Smoking status modifies the relation between CYP1A1*2C gene polymorphism and idiopathic male infertility: the importance of gene-environment interaction analysis for genetic studies of the disease.

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.