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

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Vol. 27; no. 1; pp. 29 - 38
• Main Authors: Kim, Jung Oh, Ahn, Eun Hee, Sakong, Jung Hyun, An, Hui Jeong, Park, Han Sung, Kim, Young Ran, Lee, Jung Ryeol, Lee, Woo Sik, Kim, Nam Keun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2020
• Subjects: Embryology; Medicine; Medicine & Public Health; Obstetrics/Perinatology/Midwifery; Reproductive Medicine; Review; miRNA; Recurrent implantation failure; Single nucleotide polymorphism; miR-27a; miR-449b
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1007/s43032-019-00031-6

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-27a A>G, miR-423 C>A, miR-449b A>G, and miR-604 A>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-27a A>G, miR-423 C>A, miR-449b A>G, and miR-604 A>G. We found that the miR-27a A>G, miR-449b A>G, and miR-604 A>G polymorphisms were significantly associated with a risk of RIF. In addition, the miR-27a A>G and miR-449b A>G polymorphisms were associated with the frequency of implantation failures. Specifically, the miR-449b AG+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.