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.
Highlights
Recurrent pregnancy loss (RPL), which is defined as at least two pregnancy losses (PLs) that occur before 20 weeks of gestational age [1], is a relatively common condition [2] that occurs in approximately1–5% of reproductive-aged women [1]
We investigated the relationship between four miRNA polymorphisms, miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T, and RPL, in a cohort of Korean women
The levels of E2 and luteinizing hormone (LH) were significantly higher in RPL patients than in control subjects, whereas follicle-stimulating hormone (FSH) levels were decreased in RPL subjects compared with those in control subjects
Summary
Recurrent pregnancy loss (RPL), which is defined as at least two pregnancy losses (PLs) that occur before 20 weeks of gestational age [1], is a relatively common condition [2] that occurs in approximately. Polymorphisms in microRNAs (miRNAs) have been linked to RPL. These small, non-coding RNAs are approximately 20–24 nucleotides (nt) in length and are involved in the regulation of many critical biological processes. MiRNA SNPs, such as those reported for miR-423 and miR-125a, have been associated with RPL occurrence in Chinese women [9]. In our previous studies, we found that polymorphisms in miR-150, miR-1179, miR-27a, and miR-449b were associated with an increased risk of RPL [10]. Because TGF-β superfamily members play crucial roles in female reproductive function and angiogenesis [18], we hypothesize that these miRNAs are involved in reproductive system development and/or function. To further determine whether miR-25, miR-32, miR-125, and miR-222 are associated with RPL, in this study, we selected four miRNA polymorphisms, miR-25 rs1527423 T>C, miR-32 rs7041716 C>A, miR-125a rs12976445 C>T, and miR-222 rs34678647 G>T, and measured their frequencies in Korean women with RPL and healthy controls
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