Association Between MicroRNAs Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis in Chinese Individuals

Li, Chenxi; Weng, Hong; Zheng, Jun; Feng, Zhihe; Ou, Jianlin; Liao, Weijing

doi:10.3389/fnagi.2018.00082

Cited by 21 publications

(9 citation statements)

References 39 publications

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“…Patients P1 and P3 presented the rs3746444 variant in hsa-miR-499a/b, resulting in an altered expression profile with common phenotypic features of RASopathies, congenital cardiomyopathy, and pulmonary stenosis. These data corroborate the results found in other studies that have suggested cardiovascular diseases are associated with this miRNA variant (Fawzy et al, 2018; Li et al, 2018). The miRNA hsa-miR-499 has previously been associated with the development and functioning of the heart, showing high expression in cardiac tissue, and with alterations in physiological and pathological processes during myocardial injury and remodelling (Dorn et al, 2012).…”

Section: Discussionsupporting

confidence: 92%

miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes

et al. 2019

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RASopathies are a group of rare genetic diseases caused by germline mutations in genes involved in the RAS–mitogen-activated protein kinase (RAS-MAPK) pathway. Whole-exome sequencing (WES) is a powerful approach for identifying new variants in coding and noncoding DNA sequences, including miRNAs. miRNAs are fine-tuning negative regulators of gene expression. The presence of variants in miRNAs could lead to malfunctions of regulation, resulting in diseases. Here, we identified 41 variants in mature miRNAs through WES analysis in five patients with previous clinical diagnosis of RASopathies syndromes. The pathways, biological processes, and diseases that were over-represented among the target genes of the mature miRNAs harboring variants included the RAS, MAPK, RAP1, and PIK3-Akt signaling pathways, neuronal differentiation, neurogenesis and nervous system development, congenital cardiac defects (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy), and the phenotypes and syndromes of RASopathies (Noonan syndrome, Legius syndrome, Costello syndrome, Cafe au lait spots multiple, subaortic stenosis, pulmonary valve stenosis, and LEOPARD syndrome). Furthermore, eight selected variants in nine mature miRNAs (hsa-miR-1304, hsa-miR-146a, hsa-miR-196a2, hsa-miR-499a/hsa-miR-499b, hsa-miR-449b, hsa-miR-548l, hsa-miR-575, and hsa-miR-593) may have caused alterations in the secondary structures of miRNA precursor. Selected miRNAs containing variants such as hsa-miR-146a-3p, hsa-miR-196a-3p, hsa-miR-548l, hsa-miR-449b-5p, hsa-miR-575, and hsa-miR499a-3p could regulate classical genes associated with Rasopathies and RAS-MAPK pathways, contributing to modify the expression pattern of miRNAs in patients. RT-qPCR expression analysis revealed four differentially expressed miRNAs that were downregulated: miRNA-146a-3p in P1, P2, P3, P4, and P5, miR-1304-3p in P2, P3, P4, and P5, miR-196a2-3p in P3, and miR-499b-5p in P1. miR-499a-3p was upregulated in P1, P3, and P5. These results indicate that miRNAs show different expression patterns when these variants are present in patients. Therefore, this study characterized the role of miRNAs harboring variants related to RASopathies for the first time and indicated the possible implications of these variants for phenotypes of RASopathies such as congenital cardiac defects and cardio-cerebrovascular diseases. The expression and existence of miRNA variants may be used in the study of biomarkers of the RASopathies.

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Section: Discussionsupporting

confidence: 92%

miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes

et al. 2019

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“…In agreement with our findings, Li et al22 reported that the level of miRNA 146a was significantly lower in ischemic stroke patients in the acute phase, compared to patients in the subacute phase and healthy controls. Such findings were further supported by genetic studies which demonstrated a significant association between miRNA 146a polymorphisms and the risk of ischemic stroke23,24; however, this association is still debatable 25…”

Section: Discussionmentioning

confidence: 77%

<p>The expression of microRNA 146a in patients with ischemic stroke: an observational study</p>

Kotb¹,

Ibrahim²,

Mohamed³

et al. 2019

IJGM

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Aim We conducted the present prospective study to assess the level of microRNA (miRNA) 146a in patients with ischemic stroke and its correlation with patients’ characteristics. Methods We conducted an observational study that included adult patients (≥18 years old) who presented within 24 hrs after the onset of the symptoms of acute ischemic stroke. In addition, age- and sex-matched healthy volunteers were included as control group. The primary outcome in the present study was the difference in miRNA 146a expression between patients with ischemic stroke and control group participants. The expression of miRNA 146a was measured using quantitative real-time PCR. Quantitative real-time PCR amplification and analysis were performed using Rotor-Gene Q thermal cycler. Results The present study included 44 patients with ischemic stroke and 22 matched controls. Regarding the primary outcome of the present study, the median expression of miRNA 146a in patients with ischemic stroke was −1.98 fold (IQR −27.1–3.9) compared to 1.75 fold (IQR −2.25–5.27) in control group ( P <0.001). However, the subgroup analysis showed that the expression of miRNA 146a was significantly downregulated in comatosed patients only ( P <0.001). The expression of miRNA 146a correlated negatively with Glasgow Coma Scale score in comatose patients ( r =−0.352, P =0.022). Conclusion In conclusion, the expression of miRNA 146a is significantly downregulated in ischemic stroke patients. Further studies are needed to assess its diagnostic utility and therapeutic potentials.

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“…Firstly, it disturbs miR-499 regulation of blood pressure; secondly, it hampers miR-499 anti-apoptotic effect in cardiomyocytes [105]. In a recent study by Li et al, it has been reported that the G allele of the rs3746444 is associated with ischemic stroke in the Chinese population [115]. Li et al, suggested that the association of rs3746444 with ischemic stroke because miR-499 has roles in the reduction of the activation of the mitochondrial fission program mediated by Drp1 [115], as well as it has roles in the regulation of expression of inflammatory cytokines such as C-reactive protein and interleukins [115].…”

Section: Mir-499 Rs3746444 A>gmentioning

confidence: 99%

Potential Impact of MicroRNA Gene Polymorphisms in the Pathogenesis of Diabetes and Atherosclerotic Cardiovascular Disease

Elfaki

Mir

et al. 2019

JPM

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MicroRNAs (miRNAs) are endogenous, small (18–23 nucleotides), non-coding RNA molecules. They regulate the posttranscriptional expression of their target genes. MiRNAs control vital physiological processes such as metabolism, development, differentiation, cell cycle and apoptosis. The control of the gene expression by miRNAs requires efficient binding between the miRNA and their target mRNAs. Genome-wide association studies (GWASs) have suggested the association of single-nucleotide polymorphisms (SNPs) with certain diseases in various populations. Gene polymorphisms of miRNA target sites have been implicated in diseases such as cancers, diabetes, cardiovascular and Parkinson’s disease. Likewise, gene polymorphisms of miRNAs have been reported to be associated with diseases. In this review, we discuss the SNPs in miRNA genes that have been associated with diabetes and atherosclerotic cardiovascular disease in different populations. We also discuss briefly the potential underlining mechanisms through which these SNPs increase the risk of developing these diseases.

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Association Between MicroRNAs Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis in Chinese Individuals

Cited by 21 publications

References 39 publications

miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes

miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes

<p>The expression of microRNA 146a in patients with ischemic stroke: an observational study</p>

Potential Impact of MicroRNA Gene Polymorphisms in the Pathogenesis of Diabetes and Atherosclerotic Cardiovascular Disease

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