(087) Association of ESRα T397C (rs2234693) with Male Infertility: A Meta-analysis

Abstract

Abstract Introduction Infertility is the incapability to achieve fertilization after a certain period following sexual intercourse without any contraceptive measures which affects 1 in 6 couples. Male factors contribute 50%. The male reproductive system is affected by both environmental and genetic factors. Genetics variations include chromosomal aberrations, genomic and/or mitochondrial single gene mutations or polymorphism, and multiple gene mutations or polymorphism that result in spermatogenic failure. Genetic variations of key genes might have a role in male infertility. In this regard, polymorphism in the estrogen receptor gene may be an important factor increasing the risk of male infertility. In men, estrogen is produced in the testis by Sertoli cell, Leydig cell and germ cells that play an important role in the maturation and capacitation of sperms. The action of estrogen is mediated by two specific Receptors: Estrogen receptors α (ESRα) and Estrogen receptor β (ESRβ). ESRα gene is present on chromosome 6q25. It consists of 8 exons which are parted by 7 intronic regions having a complete size of 140 kb. ESRα codes for 595 amino acid proteins. The most widely studied single nucleotide polymorphism (SNP) in ESRα is T397C (rs2234693). It is found in intron 1 and divided by 46 bp. Few previously published studies reported an association between this SNP in ESRα and male infertility, while others found no association. Objective The present study aims to estimate the association between ESRα T397C (rs2234693) and male infertility. Methods PUBMED, CENTRAL, Google Scholar and PMC articles were searched, whereas case-control, published studies regarding ESRα T397C (rs2234693) and male infertility were selected for this meta-analysis. Results Four studies finally fulfilled the criteria of the meta-analysis. No significant association (p > 0.05) was found overall, between ER alpha polymorphism and male infertility, based on all of the four genetic models. However, when stratified into two ethnic groups, ER polymorphism was found to be significantly associated with male infertility in the Caucasian group based on the dominant model (CC + CT vs TT: OR= 1.43, 95% CI [1.08-1.91], I2 = 89%) as well as recessive model (CC vs CT+TT: OR= 1.34, 95% CI [1.01-1.76], I2 = 0%), whereas, in the Asian group, only the dominant model (CC + CT vs TT: OR= 1.97, 95% CI [1.58-2.46], I2 = 98%) indicated significant association of ER alpha polymorphism with male infertility. Conclusions ESRα T397C (rs2234693) polymorphism is linked with male infertility in the two ethnic groups, i.e., homozygous conditions in Caucasian and dominant conditions in Asian populations. Disclosure No