miR-27a and miR-449b polymorphisms associated with a risk of idiopathic recurrent pregnancy loss

Abstract

ObjectiveMicroRNAs (miRNAs) regulate gene expression during the peri-implantation period. The purpose of this study was to investigate whether genetic polymorphisms in the four miRNAs associated with fetal or placental development play roles in the development of idiopathic recurrent pregnancy loss (RPL) in Korean females.Study designA case-control study involving 225 controls and 387 women with at least two consecutively recurrent pregnancy losses between 1999 and 2012 was performed. The genotypes of the four miRNA polymorphisms, including miR-27a rs895819, miR-423 rs6505162, miR-449b rs10061133, and miR-605 rs2043556, were analyzed by the polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals were estimated using multivariate analyses after maternal age adjustments. The relationships between each of the four microRNA genotypes and each of the six clinical parameters of the RPL patients (plasma homocysteine and folate levels, natural killer cell number, platelet count, prothrombin time, and, activated partial thromboplastin time) were analyzed using multiple linear regression analyses.ResultsOur results suggest that weak associations between decreased RPL risk and the genotypes of miR-27a (AG and AG+GG), combination genotype of miR-27a/miR-423 (AG/GC), and haplotypes of miR-27a/miR-423/miR-449b/miR-605 (G-C-A-G) and miR-27a/miR-449b/miR-605 (G-A-G), whereas weak associations between increased RPL risk and genotypes of miR-449b (GG and AG+GG), combination genotypes of miR-423/miR-449b (CC/GG and CA/AG), miR-449b/miR-605 (AG/AG), haplotypes of miR-27a/miR-423/miR-449b/miR-605 (A-C-G-A, A-A-A-G, and G-C-G-G), miR-27a/miR-423/miR-449b (A-C-G), miR-27a/miR-449b/miR-605 (A-A-G, A-G-A, and G-G-G), miR-423/miR-449b/miR-605 (C-G-G and A-A-G), and miR-423/miR-449b (C-G and A-A). The genotypes of miR-27a (AG and AG+GG) also showed significant contributions to the prediction of folate levels in RPL patients.ConclusionsThe study showed associations between miRNA polymorphisms (miR-27a rs895819 and miR-449b rs10061133) and RPL development, and between the miRNA polymorphism (miR-27a rs895819) and plasma folate levels.

Integrated Analysis of miRNA-mRNA Network Reveals Different Regulatory Patterns in the Endometrium of Meishan and Duroc Sows during Mid-Late Gestation

“…Some DE miRNAs identified in our study play a significant role in pregnancy loss. The miR-27a polymorphism, for example, is significantly associated with pregnancy loss in humans [52]. Consistent with our findings, Wessels et al identified miR-323 and miR-27a as potentially involved in spontaneous embryo loss in pigs [51].…”

“…We also identified 14, 36, 57, and 43 DE miRNAs (p-value < 0.05) in the four comparisons described above ( Supplementary Material Table S9). Among these, miR-19a [50], miR-323 [51], miR-27a [51,52], miR-30a-5p [53] may be involved in fetal loss during pregnancy. Venn diagrams showing the differentially expressed genes and miRNAs from the four groups are presented in Figure 1A (mRNAs) and Figure 1B Table S9).…”

MiR‐27a‐3p and miR‐124‐3p, upregulated in endometrium and serum from women affected by Chronic Endometritis, are new potential molecular markers of endometrial receptivity

“…The authors suggested that miRNAs represent a potential target for clinical sepsis research and treatment. 44 MiR-124-3p was found downregulated in endometrial cancers and recently it has been demonstrated that modified exosomes could efficiently deliver miR-124-3p to the brain and that miRNAs are able to protect against ischemic injury by robust cortical neurogenesis. 43 Finally, a recent paper reported that miR-27a-3p polymorphisms are associated with a risk of idiopathic recurrent pregnancy loss.…”

“…43 Finally, a recent paper reported that miR-27a-3p polymorphisms are associated with a risk of idiopathic recurrent pregnancy loss. 44 MiR-124-3p was found downregulated in endometrial cancers and recently it has been demonstrated that modified exosomes could efficiently deliver miR-124-3p to the brain and that miRNAs are able to protect against ischemic injury by robust cortical neurogenesis. 45,46 We found the downregulation of IGF1 and IL11 and demonstrated the anticorrelation between miR-27a-3p and IGF1 (Figure 3).…”

The ‑2549 insertion/deletion polymorphism in the promoter region of VEGF is associated with the risk of recurrent spontaneous abortion

“…A number of studies have demonstrated an association between genetic variants and the risk of RSA (27)(28)(29)(30). VEGF is among the established regulators of angiogenesis during pregnancy and has been associated with RSA (31,32).…”