Study On The Associations Between The CYP1A1 And GST Gene Polymorphisms And Male Infertility

Objective: Infertility has been a general condition for all countries, and for about half of these infertility couples, male factors are the cause of infertility. Male infertility is a complex disease caused by many reasons including genetic factors, environmental factors and the interaction of the genetic and environmental factors, etc. Nowadays, pollution has affected the human reproductive health. Xenobiotics constitute the majority of the environmental factors. To avoid the accumulation of xenobiotics in the cells and tissues, the detoxifying enzymes(CYP450 and GST) protect the body from the damage from the xenobiotics. The enzymes of cytochrome P450 catalyze phase I oxidation reactions and the enzymes encoded by GST gene participate in the phase II reactions. To date, many studies have reported the associations between the detoxification genes polymorphisms and idiopathic male infertility. But the results were inconsistent and the reasons may be the different races, sample size and the genotyping methods. The aim of the study was to explore the associations between CYP1A1(rs4646422 and rs1048943), GSTM5(rs11807), GSTM3(rs1571858, rs7483 and rs3814309) and GSTP1(rs1695) polymorphisms and idiopathic male infertility in Chinese-Han population.We also used the meta-analysis which based on the early published studies, to evaluate the associations between the detoxification genes polymorphisms and idiopathic male infertility. Method: In this study, according to the sample collection criterion, we collected 386 infertility males who come to Nanjing general hospital to see a doctor as the case group(including 153 azoospermia males and 233 oligospermia males), and the 441 healthy males were recognized as the control group. The Mass ARRAY i PLEX GOLD was used to detect the genotype in seven single nucleotide polymorphisms including CYP1A1(rs4646422 and rs1048943), GSTM5(rs11807), GSTM3(rs1571858, rs7483 and rs3814309) and GSTP1(rs1695). Odds ratio and 95% confidence interval were applied to detect the associations between detoxification genes polymorphisms and idiopathic male infertility.To further determine the associations between detoxification genes(CYP1A1 rs4646903, GSTM1 and GSTT1) polymorphisms and idiopathic male infertility, this meta-analysis was performed according to 27 published case-control studies. The odds ratio and 95% confidence interval were used to evaluate the strength of the associations between detoxification genes polymorphisms and idiopathic male infertility. Results: In this study, no statistical differences in the days of abstinence and average age between the cases and controls were present. The levels of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) in serum of cases were higher than that of the controls. For the rs7483, the GG genotype would increase the risk of male infertility compared with the AA genotype(OR=1.22, 95%CI: 1.04–2.11, P =0.023). In the subgroup analysis, the GG genotype also increased the risk in the(OR=1.27, 95%CI: 1.03–2.60, P=0.035) azoospermia and(OR=1.19, 95%CI: 1.04–2.25, P =0.013) oligospermia. For the rs3814309, the TT genotype would increase the risk of male infertility compared with the CC genotype(OR=1.22, 95%CI: 1.05–2.09, P =0.033) and significant associations were present in the comparison of TT vs. CC with male infertility in the(OR=1.23, 95% CI: 1.12–2.51, P =0.014) azoospermia and oligospermia(OR=1.21, 95%CI: 1.13–2.27, P=0.020). A significant association was found between the rs7483 and rs3814309 G-T haplotype in the haplotypic analysis(OR=1.09, 95%CI: 1.02–2.36, P =0.035). For another SNPs rs4646422, rs1048943, rs11807, rs1571858 and rs1695, no significant associations were found in all comparisons.The results of the meta-analysis revealed that CYP1A1(rs4646903) increased risks observed for the comparison of C vs. T(OR=1.36, 95%CI: 1.01–1.83, Ph=0.000), CC vs. TT(OR=2.18, 95%CI: 1.15–4.12, Ph=0.000) and CC vs. TC+TT(OR=1.86, 95%CI: 1.09–3.20, Ph=0.013). In the overall analysis, the frequency of GSTM1 null genotype(OR=1.31, 95%CI: 1.08–1.60, Ph=0.000) was significantly associated with susceptibility to idiopathic male infertility. GSTT1 null genotype(OR=1.31, 95%CI: 1.02–1.68, Ph=0.000) also revealed the association. Conclusion: In this study, we found GSTM3 rs7483 GG genotype increased the risk of male infertility; GSTM3 rs3814309 TT also increased the risk of male infertility in Chinese-Han population.The results of meta-analysis indicated the CYP1A1(rs4646903) CC genotype increased the risk of male infertility. GSTM1 and GSTT1 null genotype also increased the risk of idiopathic male infertility. The above results suggested a gene polymorphism research should be carried out at different SNPs.