Association of the miR-146a , miR-149 , miR-196a2 , and miR-499 Polymorphisms With Ischemic Stroke and Silent Brain Infarction Risk

Abstract

Objective— MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of miR-146a , miR-149 , miR-196a2 , and miR-499 polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported. Methods and Results— Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The miR-146a C>G polymorphism and miR-146a G/ -149 T/ -196a2 C/ -499 G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of miR-146a / -149 / -196a2 / -499 ). In subgroup analyses, miR-146a C>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence. Conclusion— The miR-146a G allele and miR-146a G/ -149 T/ -196a2 C/ -499 G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.

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

“…Moreover, previous studies have indicated that temporal miRNA regulation may be related to the progression of ischemia in the cerebral artery (17,18). Furthermore, a recent study found a significant association between miRNA single nucleotide poly-morphisms (SNPs) and the risk of ischemic stroke (19). As has been previously reported by Edelstein et al (20), as regards the regulated function of megakaryocytopoiesis, various miRNAs play a crucial role in this process, as well as in platelet biogenesis.…”

A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population

“…The homozygous GG genotype exerted no noticeable effect on the susceptibility in this study, which might be due to the limited sample size of subjects with GG genotype (only 18.3% or 19.8% in the populations). The miR-146a C>G polymorphism has also been reported to associate with the risk of ischemic stroke (Jeon et al 2013;Huang et al 2015), which indicates that ACS or CHD may share genetic risk factors with ischemic stroke. Although rs11614913 was associated with an increased risk of ACS in the females, we found no association in the whole population.…”

MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype

“…Excitingly, the understanding of the genetic risks associated with vascular disease has expanded to include the observation that polymorphisms in microRNA genes or microRNA-binding by guest on May 11, 2018 http://atvb.ahajournals.org/ Downloaded from sites in critical protein-coding genes can contribute to pathogenesis of vascular disease. 56 Recently, Jeon et al 57 found that single nucleotide variation in the miRs-146a, -149, -196a-2, and -499 were significantly associated with stroke prevalence in a Korean population, and the authors surmise this may be because of decreased expression of inflammatory mediators, such as TNFα and CRP. Although the field of microRNAs as biomarkers is continuing to evolve, there is little doubt that their use for the prediction and diagnosis of vascular disease will be significant.…”