title: A role of pre-mir-10a coding region variant in host susceptibility to coxsackie virus-induced myocarditis.
abstract: OBJECTIVE
  Acute viral myocarditis (VM) is an important cause of sudden cardiac death and heart failure in healthy young person. Direct virus-mediated injury and secondary immune reactions, including inflammatory and autoimmune responses, have been reported both in animal models and in humans. Recently, genetic variation has been confirmed related to myocarditis process and susceptibility to VM. In this study, we scanned 339bp of pri-miR-10a coding region in CVB3 VM patients, want to found genetic relations between miR-10a and VM susceptibility.
  
  
  METHODS
  The secondary structure of two genotype 220 bp pri-miR-10a sequences was predicted using RNAfold web server. In vitro biological functional study concluded dual luciferase assay and Western blotting.
  
  
  RESULTS
  We found the rare allele T of rs3809783 was accumulated in VM patients and related to VM significantly. Subsequently, we confirmed that ITCH, a NK-κB signaling suppressor, is a direct target of miR-10a. In vitro biological functional study indicated that this site variation reduced mature miR-10a expression and induced a down-regulated cytokine secretion in the cell culture supernatant.
  
  
  CONCLUSIONS
  The results suggest that the rare allele T in pri-miR-10a coding region should be involved in the CVB3 caused VM pathogenesis through weakening host anti-virus immune response. This site may be used for clinical genetic evaluation for VM susceptibility.
authors.affiliation: Department of Cardiology, the Affiliated Longyan First Hospital of Fujian Medical University, Longyan, Fujian, China. liaoy_ly@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Liao
authors.forename: K-H
authors.initials: KH
authors.lastname: Chen
authors.forename: X-M
authors.initials: XM
authors.lastname: Dong
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
authors.forename: W-G
authors.initials: WG
authors.lastname: Li
authors.forename: G-Y
authors.initials: GY
authors.lastname: Huang
authors.forename: W
authors.initials: W
authors.lastname: Song
mesh_terms: D000208:Acute Disease; D000368:Aged; D000818:Animals; D018929:Cell Culture Techniques; D003384:Coxsackievirus Infections / Q000235:genetics*; D004198:Disease Susceptibility; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009205:Myocarditis / Q000235:genetics*
chemical_list: D035683:MicroRNAs