title: 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.
  
  
  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-146aC>G polymorphism and miR-146aG/-149T/-196a2C/-499G 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-146aC>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.
  
  
  CONCLUSIONS
  The miR-146aG allele and miR-146aG/-149T/-196a2C/-499G 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.
authors.affiliation: Institute for Clinical Research, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Ok Joon
authors.initials: OJ
authors.lastname: Kim
authors.forename: Su Yeoun
authors.initials: SY
authors.lastname: Kim
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Oh
authors.forename: Doyeun
authors.initials: D
authors.lastname: Oh
authors.forename: Ok Jun
authors.initials: OJ
authors.lastname: Kim
authors.forename: Byoung Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D020520:Brain Infarction / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004843:Epistasis, Genetic; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C542542:MIRN146 microRNA, human; C551557:MIRN149 microRNA, human; C542543:MIRN196 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D006710:Homocysteine; D005492:Folic Acid