Abstract

The microRNA (miRNA) is a small non-coding RNA molecule that modulates gene expression at the posttranscriptional level. Platelets have a crucial role in both hemostasis and thrombosis, a condition that can occlude a cerebral artery and cause ischemic stroke. miR-130b, miR-200b, and miR-495 are potential genetic modulators involving platelet production and activation. We hypothesized that single nucleotide polymorphisms (SNPs) in these miRNAs might potentially contribute to the susceptibility to ischemic stroke and post-stroke mortality. This study included 523 ischemic stroke patients and 400 control subjects. We investigated the association of three miRNA SNPs (miR-130bT>C, miR-200bT>C, and miR-495A>C) with ischemic stroke prevalence and post-stroke mortality. In the multivariate logistic regression, there was no statistically significant difference in the distribution of miR-130bT>C, miR-200bT>C, or miR-495A>C between the ischemic stroke and control groups. In the subgroup analysis based on ischemic stroke subtype, the miR-200b CC genotype was less frequently found in the large-artery atherosclerosis stroke subtype compared with controls (TT+CT vs CC; adjusted odds ratio for CC, 0.506; 95% confidence interval, 0.265–0.965). During a mean follow-up period of 4.80 ± 2.11 years after stroke onset, there were 106 all-cause deaths among the 523 stroke patients. Multivariate Cox regression analysis did not find a significant association between post-stroke mortality and three miRNA SNPs. Our findings suggest that the functional SNP of miR-200b might be responsible for the susceptibility to large-artery atherosclerotic stroke.

Highlights

  • Stroke is a major public health issue and a leading cause of death and disability worldwide [1]

  • In a prior study of the expression pattern of miRNA during platelet production and differentiation, miR-130b, miR-200b, and miR-495 were found to be significantly down-regulated during megakaryocyte maturation [11]. miR-130 targets MAFB, a transcription factor required for promoting platelet development [12,13,14]. miR-200b and miR-495 knocked down PRKAR2B and kelch-like family member 5 (KLHL5), respectively, and both are platelet functional proteins [15]

  • In this study comprising over 900 Korean subjects, we explored the susceptibility to ischemic stroke and mortality after ischemic stroke according to these miRNA single nucleotide polymorphisms (SNPs)

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Summary

Introduction

Stroke is a major public health issue and a leading cause of death and disability worldwide [1]. Increased platelet activity is a predisposing factor to the formation of thrombi and the occurrence of acute vascular diseases such as myocardial infarction and ischemic stroke [3, 4]. Altered miRNA regulation has been implicated in the pathogenesis of various disorders including stroke. A large number of miRNAs are expressed in platelets, and miRNA expression profiles vary with platelet biogenesis, maturation, and activation [6, 7]. This dynamic miRNA expression in platelets is considered a novel genetic regulatory pathway for platelet formation and activation, and might be an underlying pathway for the pathogenesis of thrombotic disorders [8,9,10]. MiR-495 was up-regulated with thrombin stimulation compared with the expression in the resting condition [16]

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