Association study of novel single nucleotide polymorphisms of androgen receptor and estrogen receptor-α genes with male infertility in Northwest of Iran: A case-control study

Background: Observational evidence on the association of novel single nucleotide polymorphisms (SNPs) of androgen receptor (AR) and estrogen receptor-α (ER-α) genes with odds of male infertility are rare. This is particularly relevant in the Iranian population where male infertility is relatively high. Objective: This study was designed to investigate the relationship between different SNPs of these genes and male infertility among the Iranian population. Materials and Methods: The present project was a population-based, case-control study conducted on 120 idiopathic azoospermia or severe oligospermia infertile cases alongside 120 age-matched subjects enrolled as controls. Overall, 3 variants from the AR gene and 2 variants from ER-α were genotyped - AR rs137852568, AR rs137852599 and AR rs137852563, and ER-α rs796065354 and ER-α rs104893956 - using amplification refractory mutation system methods. Results: The obtained results indicated a significant association between AR rs1378525568 TT genotype as well as AR rs137852599 C allele with odds of male infertility (OR: 0.433, CI: 0.197-0.951 and OR: 0.545, CI: 0.304-0.978, respectively). Other variants of AR were not related to male infertility. A significant association was noted between predisposition polymorphism ER-α rs796065354 genotypes with male infertility. This significant association was not seen between ER-α rs104893956 and the risk of idiopathic azoospermia or severe oligospermia. Heterozygote overdominance was also observed in ESR rs796065354 but not in the other variants studied. Conclusion: Pieces of evidence were found on the association of novel polymorphisms of AR and ER-α with male infertility among the Iranian population. However, larger studies are warranted to confirm our findings. Key words: Male infertility, Androgen receptor, Estrogen receptor-α.