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
Department of Biomedical Science, College of Life Science, CHA University, Seongnam, 13488, South Korea.
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam, 13496, South Korea.
Reprod Sci. 2020 Jan;27(1):29-38. doi: 10.1007/s43032-019-00031-6. Epub 2020 Jan 1.
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.
复发性植入失败（RIF）的定义是，在女性连续两次将至少四个高质量胚胎体外受精-胚胎移植到子宫内膜后仍发生妊娠失败。微小RNA是众所周知的功能调节剂，参与多种疾病。最近，关于微小RNA与复发性流产（RPL）的研究一直在积极开展；然而，RPL中miRNA的单核苷酸多态性尚不清楚。因此，我们开展本研究的目的是确定miR-27aA>G、miR-423C>A、miR-449bA>G和miR-604A>G这些miRNA中的多态性是否是韩国女性特发性复发性植入失败（RIF）的危险因素。采用聚合酶链反应-限制性片段长度多态性分析进行基因分型。我们检测了四个miRNA基因中的多态性：miR-27aA>G、miR-423C>A、miR-449bA>G和miR-604A>G。我们发现miR-27aA>G、miR-449bA>G和miR-604A>G多态性与RIF风险显著相关。此外，miR-27aA>G和miR-449bA>G多态性与植入失败频率相关。具体而言，miR-449bAG+GG基因型与RIF患病率相关（总RIF：调整后的优势比[AOR]=1.584，95%置信区间[CI]=1.008-2.490，P=0.046；IF≥3组：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）。基于这些结果，miR-449b A>G可能是RIF易感性的一个易感因素。然而，miR-449b A>G在RIF中的功能机制仍有待确定，需要进一步研究以更好地理解miR-449b A>G的作用，研究应使用更大且更具异质性的队列。
