Influence of miRNA Gene Polymorphism on Recurrence and Age at Onset of Ischemic Stroke in a Chinese Han Population

Neurotox Res. 2020 Apr;37(4):781-787. doi: 10.1007/s12640-019-00125-8. Epub 2019 Dec 6.

Abstract

Polymorphisms in microRNAs (miRNAs) are associated with ischemic stroke occurrence and traditional risk factors for ischemic stroke such as atherosclerosis, hypertension, hyperlipidemia, and diabetes. However, few studies have examined recurrent ischemic stroke as an outcome. Thus, the aim of our study was to examine association of miRNA gene polymorphisms (namely, miR-126 rs4636297, miR-149 rs2292832, miR-124 rs531564, miR-499 rs3746444, miR-143 rs12655723, and miR-122 rs17669) with recurrence of ischemic stroke. miRNA gene polymorphisms were genotyped using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method in 657 patients with ischemic stroke. Association of miRNA polymorphisms with prognosis outcomes was examined by the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. miR-122 rs17669 was significantly associated with recurrence risk of ischemic stroke under the recessive model. Cox regression analysis showed that the CC genotype of rs17669 was associated with an increased risk of 1.9-fold for stroke recurrence (hazard ratio = 1.879; 95% confidence interval = 1.182-2.985; P = 0.008). Further, this effect was more evident among the non-drinker and male subgroups. We found no difference in risk of recurrent ischemic stroke among the other five miRNA polymorphisms. Furthermore, we identified a significant association between the miR-149 rs2292832 polymorphism and age at onset of first-ever stroke. Altogether, miR-122 rs17669 is a significant predictor for the risk of recurrent stroke, independent of traditional risk factors.

Keywords: Ischemic stroke; Polymorphism; Recurrence; miRNA.

MeSH terms

  • Age of Onset
  • Aged
  • Asian People / ethnology
  • Asian People / genetics*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Ischemic Stroke / ethnology
  • Ischemic Stroke / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Recurrence

Substances

  • MicroRNAs