Study of the Association between microRNA (miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T) Polymorphisms and the Risk of Recurrent Pregnancy Loss in Korean Women

Abstract

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; P = 0.003). Three-gene combinations, including miR-32C/miR-125aT/miR-222T (AOR, 3.085; 95% CI, 1.254–7.588; P = 0.010) and miR-25T/miR-125aT/miR-222T (AOR, 2.929; 95% CI, 1.183–7.257; P = 0.015), and the two-gene combination miR-125aT/miR-222T (AOR, 2.417; 95% CI, 1.084–5.386; P = 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 (P < 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.

Association Study between Mucin 4 (MUC4) Polymorphisms and Idiopathic Recurrent Pregnancy Loss in a Korean Population

“…Moreover, environmental factors such as infection, smoking, alcohol, psychological trauma, and stress may contribute to RPL [ 8 , 9 , 10 ]. However, the cause of RPL is unclear in 30–40% of cases, and recent studies suggest that genetic factors play an important role in the pathogenesis of idiopathic RPL [ 11 , 12 ].…”

Non‐coding RNAs and their cross‐talks impacting reproductive health of women

“…Additional findings revealed the involvement of miR‐326 in intrauterine adhesion, leading to infertility and pregnancy loss, here it was deciphered that the said miRNA negatively regulates the TGF‐β1/Smad3 pathway by targeting TGF‐β1, suggesting its vital role as a prognostic marker and as a therapeutic target (Ning et al, 2018). Furthermore, structural changes, such as nucleotide polymorphisms in miRNAs, can also lead to pregnancy loss by modulating target selection that impacts pregnancy outcomes influencing proliferation, invasion, migration, and embryonic development pathways (Jeon et al, 2012; Lee et al, 2020; X. Q. Wang, Li, et al, 2018). However, only a handful of studies have shown dysregulated expression of lncRNAs responsible for URPL by altering numerous biological pathways, among which the majority are inflammatory and infection pathways genes (Z. Huang, Du, et al, 2018; Wang et al, 2014).…”

miRNAs in decidual NK cells: regulators worthy of attention during pregnancy

“…Currently, a clinical need exists for predictive biomarkers of pregnancy complications, such as RPL [75]. The number of NK cells has already become a clinical reference index for RPL [76], and several circulating miRNAs are also known to be differentially expressed in RPL patients when compared with healthy individuals, acting as potential biomarker candidates [77,78]. But whether differentially expressed miRNAs in NK cells can be able to more accurately discern normal individuals from those with pregnancy related disorders should be revealed in more in-depth studies.…”