Abstract
MicroRNA plays an important role in spermatogenesis. Whether pre-miRNAs polymorphisms are associated with idiopathic male infertility remains obscure. In this study, 1378 idiopathic infertile males and 486 fertile controls were included between 2006 and 2014. Genotype of three polymorphisms (hsa-mir-146a rs2910164, hsa-mir-196a-2 rs11614913, and hsa-mir-499 rs3746444) and expression of miRNA in seminal plasma were examined by TaqMan method. The role of hsa-miR-196a-5p in cell proliferation, apoptosis and cell cycle were also examined in GC-2 cells. Our results demonstrated that rs11614913 of hsa-miR-196a-2 was significantly associated with idiopathic infertility (TT vs. CT: P = 0.014; TT vs. CC: P = 0.005; TT vs. CT + CC: P = 0.003). In following stratified analysis, we found that rs11614913 exhibited a significantly higher risk of asthenospermia, oligozoospermia and azoospermia. However, no significant association was observed between the other two polymorphisms and idiopathic male infertility risk. In a genotype-expression correlation analysis, rs11614913 CC was significantly associated with elevated expression of hsa-miR-196a-5p (P < 0.05). Additionally, apoptosis levels were significantly increased in hsa-miR-196a-5p mimic treated GC-2 cells, while decreased in hsa-miR-196a-5p inhibitor treated GC-2 cells. Our data revealed a significant relationship between hsa-miR-196a-2 polymorphism and idiopathic male infertility.
Highlights
MicroRNAs are small single stranded regulatory RNAs that are produced through a multistep process generating a primary transcript-miRNA and a precursor-miRNA
The observed genotype frequencies for these three polymorphisms were all in agreement with that expected under the Hardy-Weinberg equilibrium in the controls, except for rs2910164 (P < 0.010)
It has been identified that alteration of miRNAs caused by single nucleotide polymorphisms (SNPs) plays a crucial role in various diseases, there has been no study concerning the potential role of SNPs in miRNA genes in idiopathic male infertility
Summary
MicroRNAs (miRNAs) are small single stranded regulatory RNAs that are produced through a multistep process generating a primary transcript-miRNA (pri-miRNA) and a precursor-miRNA (pre-miRNA). Hu et al performed a screening for common SNPs in miRNA sequence and have identified four SNPs (rs2910164, rs2292832, rs11614913, and rs3746444) located at the pre-miRNA regions of hsa-mir-146a, hsa-mir-149, hsa-mir-196a-2, and hsa-mir-499, respectively[11] They observed the association of the rs11614913: T > C variant genotype with a significantly increased risk of non-small cell lung cancer. We hypothesized that these functional SNPs were associated with idiopathic male infertility To validated this hypothesis, we performed genotyping analyses for rs11614913 T > C and the other two common SNPs (rs2910164 G > C, and rs3746444 A > G) located at pre-miRNA regions and evaluated their association with the susceptibility of idiopathic male infertility in a case-control study of 1378 infertility cases and 486 fertile controls in a Han Chinese population
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