A single nucleotide polymorphism in a miR-1302 binding site in CGA increases the risk of idiopathic male infertility

Abstract

To explore the possible association between single nucleotide polymorphisms (SNPs) in the miRNA-binding sites of spermatogenesis-related genes and idiopathic infertility in humans. Prospective study. Research laboratory of a university hospital. A total of 494 patients with azoospermia or severe oligozoospermia and 357 fertile controls were included in our study. The 3' untranslated region sequences of 140 candidate genes for male infertility were analyzed using specialized algorithms including Pictar, miRanda, Targetscan, and RNAhybrid and 39 SNPs located at putative miRNA-binding sites were identified. The possible association of 6 putatively functional SNPs and male infertility was explored further with the use of case-control studies. The function of SNPs significantly associated with male infertility was analyzed by dual luciferase assay. Significantly associated SNPs and their influence on gene expression. Two SNPs from two genes (rs6631 of CGA and rs2303846 of CPEB1) were found to be associated with idiopathic male infertility. Functionally, the substitution of A by T in rs6631 results in decreased binding affinity of miR-1302 and overexpression of CGA in vitro. Our results reveal for the first time that SNPs residing in miRNA-binding sites of CGA could influence expression of CGA and elevate the risk of spermatogenesis impairment.