Lee Jeong Yong, Kim Jung Oh, Park Han Sung, Ryu Chang Soo, Kim Ji Hyang, Kim Young Ran, Lee Woo Sik, Lee Jung Ryeol, Kim Nam Keun
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea.
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea.
Genes (Basel). 2020 Mar 26;11(4):354. doi: 10.3390/genes11040354.
Recurrent pregnancy loss (RPL), which is defined as two pregnancy losses that occur before 20 weeks of gestation, is relatively common, occurring in approximately 1-5% of women. The underlying cause is often unclear, although numerous factors may contribute to RPL, including environmental and immunological factors, blood coagulation disorders, and genetics. In particular, single nucleotide variants have been associated with RPL, including those found in microRNAs (miRNAs). We investigated the association between four miRNA polymorphisms, miR-25T>C, miR-32C>A, miR-125aC>T, and miR-222G>T, and RPL in a cohort consisting of 361 RPL patients and 272 controls. Subjects were genotyped at miRNA loci by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and genotype frequencies were calculated. We then performed allele and genotype combination analyses and measured the association between miRNA polymorphisms and clinical variables in both RPL patients and controls. We detected a statistically significant association between RPL and the miR-25T/miR-32C/miR-125aT/miR-222T allele combination (adjusted odds ratio (AOR), 4.361; 95% confidence interval (CI), 1.496-12.72; =0.003). Three-gene combinations, including miR-32C/miR-125aT/miR-222T (AOR, 3.085; 95% CI, 1.254-7.588; =0.010) and miR-25T/miR-125aT/miR-222T (AOR, 2.929; 95% CI, 1.183-7.257; 0.015), and the two-gene combination miR-125aT/miR-222T (AOR, 2.417; 95% CI, 1.084-5.386; 0.026) were also associated with RPL. Analysis of variance (ANOVA) revealed that platelet counts and blood urea nitrogen levels were significantly different in RPL patients expressing different miR-125aC>T and miR-25T>C genotypes, respectively (<0.05). In addition, creatinine levels were lower in RPL patients expressing the minor alleles miR-25T>C and miR-32C>A. We investigated miRNAs (miR-25, miR-32, miR-125a, miR-222) in RPL patients and healthy controls. Significantly different allele frequencies were detected by ANOVA. We suggest that miRNAs and clinical factors can impact RPL occurrence.
复发性流产（RPL）定义为妊娠20周前发生的两次流产，相对常见，约1%-5%的女性会出现。尽管许多因素可能导致复发性流产，包括环境和免疫因素、凝血障碍及遗传因素，但其根本原因通常尚不清楚。特别是，单核苷酸变异与复发性流产有关，包括在微小RNA（miRNA）中发现的变异。我们在一个由361例复发性流产患者和272例对照组成的队列中，研究了四种miRNA多态性（miR-25T>C、miR-32C>A、miR-125aC>T和miR-222G>T）与复发性流产之间的关联。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对受试者的miRNA位点进行基因分型，并计算基因型频率。然后，我们进行等位基因和基因型组合分析，并测量复发性流产患者和对照中miRNA多态性与临床变量之间的关联。我们检测到复发性流产与miR-25T/miR-32C/miR-125aT/miR-222T等位基因组合之间存在统计学显著关联（校正比值比（AOR）为4.361；95%置信区间（CI）为1.496-12.72；P=0.003）。三种基因组合，包括miR-32C/miR-125aT/miR-222T（AOR为3.085；95%CI为1.254-7.588；P=0.010）和miR-25T/miR-125aT/miR-222T（AOR为2.929；95%CI为1.183-7.257；P=0.015），以及双基因组合miR-125aT/miR-222T（AOR为2.417；95%CI为1.084-5.386；P=0.026）也与复发性流产有关。方差分析（ANOVA）显示，分别表达不同miR-125aC>T和miR-25T>C基因型的复发性流产患者的血小板计数和血尿素氮水平存在显著差异（P<0.05）。此外，表达次要等位基因miR-25T>C和miR-32C>A的复发性流产患者的肌酐水平较低。我们研究了复发性流产患者和健康对照中的miRNA（miR-25、miR-32、miR-125a、miR-222）。通过方差分析检测到显著不同的等位基因频率。我们认为miRNA和临床因素会影响复发性流产的发生。
