miR-222 and miR-146a Variants in Idiopathic Male Infertility: A Case-Control Study.

Abstract

Background: Idiopathic Male Infertility is a widespread problem affecting approximately 10 to 15 percent of men of reproductive age. Several genes have been studied related to idiopathic male infertility. Thereafter, among the family of non-coding RNAs, microRNAs are shown to play a very important role in the regulation of a subset of genes. It has been documented that infertile men have differentially expressed miRNA. The aim of this study is to evaluate the impact of two genetic variants, miR-222 rs2858060 and miR-146a rs2910164 on idiopathic male infertility.

Materials and methods: In this case-control study, Blood samples were taken from 201 men with idiopathic infertility and 201 men in a healthy state for this case-control investigation. Genotype determination of desired polymorphisms was done using the Tetra-ARMS PCR technique and data was analyzed by SPSS software version 20. Significant associations were determined at an alpha level of 0.05.

Results: The study found a significant association between the miR-222 rs2858060 GG genotype and idiopathic male infertility in the recessive genetic model [odds ratio (OR)=2.02, 95% confidence interval (CI)=1.25-3.24, P=0.004]. After adjusting for age, body mass index (BMI), smoking, and alcohol consumption, the association between the genotypes and the disease remained significant. No significant association was observed between miR-146a rs2910164 genotypes and male infertility in all genetic models (P>0.05). Moreover, haplotype analysis showed that the CC (rs2858060/ rs2910164) haplotype is associated with the decreased risk of idiopathic male infertility (OR=0.728, 95% CI =0.54-0.98, P=0.035).

Conclusion: miR-222 rs2858060 and miR-146a rs2910164 polymorphisms influence the risk of male infertility in Iranian population. This is the first report to examine the role of miR-222 rs2858060 and miR-146a rs2910164 in male infertility, further studies involving different ethnicity and larger sample sizes are needed to confirm our findings.