Association of miR-27aA>G, miR-423C>a, miR-449bA>G, and miR-604A>G Polymorphisms with Risk of Recurrent Implantation Failure

Abstract

Recurrent implantation failure (RIF) is defined when pregnancy failure occurs after two consecutive in vitro fertilization-embryo transfers to the endometrium using at least four high-quality embryos in women. MicroRNAs are well-known function modulators and are involved in many diseases. Recently, studies on microRNA and recurrent pregnancy loss (RPL) have been actively carried out; however, single nucleotide polymorphisms of miRNA in RPL are not well known. Therefore, we set the aim of this study to identify whether polymorphisms in miRNAs that miR-27aA>G, miR-423C>A, miR-449bA>G, and miR-604A>G are risk factors for idiopathic recurrent implantation failure (RIF) in Korean women. Genotyping was assessed with a polymerase chain reaction-restriction fragment length polymorphism assay. We examined polymorphisms in four miRNA genes: miR-27aA>G, miR-423C>A, miR-449bA>G, and miR-604A>G. We found that the miR-27aA>G, miR-449bA>G, and miR-604A>G polymorphisms were significantly associated with a risk of RIF. In addition, the miR-27aA>G and miR-449bA>G polymorphisms were associated with the frequency of implantation failures. Specifically, the miR-449bAG+GG genotype was associated with RIF prevalence (total RIF: adjusted odd ratio [AOR] = 1.584, 95% CI = 1.008-2.490, P = 0.046; IF ≥ 3 group: AOR = 1.747, 95% CI = 1.088-2.803, P = 0.021; IF ≥ 4: AOR = 1.932, 95% CI = 1.122-3.327, P = 0.018). Based on these results, the miR-449b A>G may be a predisposing factor to RIF susceptibility. However, the mechanism underlying the function of miR-449b A>G in RIF remains to be determined and further studies are needed to improve understanding of the roles of miR-449b A>G, using a larger and more heterogeneous cohort.

Keywords: Recurrent implantation failure; Single nucleotide polymorphism; miR-27a; miR-449b; miRNA.