Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study

Abstract

It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC ( OR = 0.029 ) and allelic C vs. T ( OR = 0.028 ) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA ( OR = 2.81 for rs2961920) and codominant GG vs. AA ( OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.

Maternal candidate gene variants, epigenetic factors, and susceptibility to idiopathic recurrent pregnancy loss: A systematic review

“…More than 65 genetic variants in 45 genes were identified that could be considered as risk factors for iRPL (Table 1). 13–59 The time frame of the sample is not mentioned in the studies because it does not involve a variable marker. Epigenetic factors, mainly microRNAs (miRNAs), that could also be considered as risk factors are compiled in Table 2 60–64 .…”

Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review

“…Table 1 summarizes the observed ncRNA expression levels and their related potential mechanisms of action in GO pathogenesis. Among the ncRNAs implicated in inflammatory regulation was miR-146a [ 80 , 81 ], LPAL2/miR-1287–5p axis, LINC01820:13/has-miR-27b-3p axis, and ENST00000499452/hsa-miR-27a-3p axis ( Fig. 4 a).…”

Estimation on risk of spontaneous abortions by genomic disorders from a meta‐analysis of microarray results on large case series of pregnancy losses

“…A recent exome sequencing study on a cohort of POC indicated that genes with dominant effect on multisystem abnormalities, neurodevelopmental disorders, cardiac anomalies, skeletal dysplasia, metabolic disorders, and renal diseases could cause SAB (Zhao et al, 2021 ). Furthermore, maternal genetic polymorphisms and fetal microRNA polymorphisms associating with immunological responses, thrombophilia, abnormal placental function, and disturbance of metabolic regulation could have a modifying effect on the penetrance of SAB for chromosomal abnormalities and pCNVs (Salimi et al, 2022 ; Shi et al, 2017 ).An integrated approach should be applied to elucidate the dosage‐sensitive effect, dominant lethal conditions, genetic modifiers, and epigenetic changes related to pregnancy losses.…”