Association of miR-34a, miR-130a, miR-150 and miR-155 polymorphisms with the risk of ischemic stroke

Int J Mol Med. 2016 Jul;38(1):345-56. doi: 10.3892/ijmm.2016.2609. Epub 2016 May 25.

Abstract

MicroRNAs (miRNAs or miRs) are small (19-23 nt) non-coding RNA molecules that are endogenous regulators of gene expression. Previous studies have found that some miRNAs are related to the progression of ischemia in the cerebral artery. Furthermore, a recent study found a significant association between miRNA single nucleotide polymorphisms (SNPs) and the risk of ischemic stroke. Therefore, it may be valuable to investigate associations between megakaryocyte formation-related miRNA polymorphisms and the prevalence of ischemic stroke. We thus conducted a case-control study of 1,000 individuals who were screened for 4 miRNA polymorphisms (miR‑34a rs6577555C>A, miR-130a rs731384C>T, miR-150 rs73056059G>A and miR‑155 rs767649T>A) by PCR-RFLP analysis. The study population comprised 596 patients with ischemic stroke and 404 control subjects without any history of neurological disorders. We observed associations between miRNA polymorphisms and individual stroke subtypes. The miR‑150 polymorphisms were significantly associated with ischemic stroke subgroups, such as left anterior descending artery (LAD) disease [GG vs. AA: adjusted odds ratio (AOR), 1.922; 95% confidence interval (CI), 1.003-3.681] and cardioembolism (GG vs. AA: AOR, 2.996; 95% CI, 1.293-6.939). Additionally, Cox proportional analysis indicated that the miR‑150GA genotype was associated with survival in patients with ischemic stroke [adjusted hazard ratio (HR), 2.063; 95% CI, 1.142-3.727; P=0.017] and with the LAD subgroup [adjusted HR, 3.021; 95% CI, 1.345-6.785; P=0.008]. Our findings suggest that miR‑150 polymorphisms may contribute to the development of ischemic stroke and may potentially act as biomarkers to predict the risk of ischemic stroke. To the best of our knowledge, this is the first study to evaluate the association between miRNA polymorphisms (miR-34aC>A, miR-130aC>T, miR-150G>A and miR-155T>A) and ischemic stroke.

MeSH terms

  • Alleles
  • Brain Ischemia / complications*
  • Case-Control Studies
  • Female
  • Gene Frequency / genetics
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Multifactor Dimensionality Reduction
  • Polymorphism, Single Nucleotide / genetics*
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / etiology*
  • Stroke / genetics*
  • Survival Analysis

Substances

  • MicroRNAs