Association of the<i>miR-146a</i>,<i>miR-149</i>,<i>miR-196a2</i>, and<i>miR-499</i>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&gt;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&gt;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.