Studies On The Association Of Polymorphisms In CYP1A1 Gene And P53 Gene With Male Infertility

Approximately 10% couples of childbearing ages suffer from some kinds of infertility, and about half of these cases are due to male factors. Previous reports from clinics confirmed that a significant proportion of male infertility is idiopathic infertility, typified by non-obstructive azoospermia or sever oligozoospermia. Many environmental, behavioral and genetic factors affect male infertility. Many genes have been suggested to be involved in spermetogenesis and it is possible that mutations in these genes are also related to human infertility.Single nucleotide polymorphisms are the most common genetic varients. Recently, several studies have focused on the association of polymorphisms with male infertility, especially with spermatogenetic failure. Thus, some gene involved in spermetogenesis may be associated with male infertility. A case-control study was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to study the association of polymorphisms in CYP1A1 gene and p53 gene with male infertility. PartⅠStudy on polymorphisms in CYP1A1 gene and male infertilityCytocrome P4501A1 (CYP1A1) is a key enzyme in phaseⅠbioactivation of polycyclic aromatic hydrocarbons (PAHs) which have potential reproductive toxicity. The aim of this study was to investigate the association of the CYP1A1 polymorphisms with male infertility in a Han-Chinese population. We genotyped two polymorphisms, CYP1A1*2A and CYP1A1*2C, using PCR-RFLP assay in a hospital-based case-control study including 192 infertile patients with non-obstructive azoospermia or severe oligozoospermia, 143 normospermic infertile men and 226 fertile controls. We found that the genotype distribution of CYP1A1*2C was significantly different between the patients with non-obstructive azoospermia or severe oligozoospermia and controls (P=0.019). Analysis showed that CYP1A1*2C AG genotype was associated with a significantly decreased risk of male infertility with azoospermia or severe oligozoospermia [odds ratio (OR)= 0.56, 95% confidence interval (95% CI)=0.36-0.86, P=0.005] compared with the AA genotype. A statistically significantly decreased risk of male infertility was found to be associated with the CYP1A1*2C AG genotype plus GG genotype compared with CYP1A1*2C AA genotype (OR=0.60, 95% CI=0.40-0.91, P=0.011). No significant association was detected between CYP1A1*2A polymorphism and male infertility. Haplotypic analysis showed a significantly decreased risk of male infertility with azoospermia or severe oligozoospermia associated with the T-G haplotype compared with the C-A haplotype (OR=0.38, 95% CI=0.16-0.87), indicating a synergic effect of those two polymorphisms. Normospermic infertile patients with CYP1A1*2C AG genotype was found to be associated with higher sperm concentration, the total sperm count and motility when compared to those with AA genotype (P=0.049, P=0.016 and P=0.049). Our results suggest that the CYP1A1 polymorphisms may contribute to the pathogenesis of male infertility in Han-Chinese population.PartⅡStudy on polymorphisms in p53 gene and male infertilityAlthough various genetic factors have been demonstrated in human male infertility, many genetic causes involving gene variants for the idiopathic male infertility have not yet been elucidated. The involvement of p53 gene in the meiosis of the male rat and mice suggested that p53 plays a critical role in spermatogenesis. To examine whether the codon72 polymorphism and IVS7+72C＞T polymorphism of the human p53 gene are associated with spermatogenetic failure in Han-Chinese population. A case-control study was conducted with 198 idiopathic infertile patients with non-obstructive azoospermia or severe oligozoospermia and 233 fertile controls. We genotyped the two polymorphisms, codon72 and IVST+72C＞T, using PCR-RFLP assay. The polymorphisms were identified in both infertile patients and fertile controls. We found no significant difference in the allelic and genotypic distributions of the two polymorphisms between the patients and controls. Further analysis showed that there was no statistically significant difference in the haplotype distributions between the patients and controls. The results of this study suggest that the codon72 and IVS7+72C＞T polymorphisms of the p53 gene are unlikely to contribute to the pathogenesis of idiopathic male infertility with spermatogenetic failure.