title: Variants of the interferon regulatory factor 5 gene regulate expression of IRF5 mRNA in atherosclerotic tissue but are not associated with myocardial infarction.
abstract: BACKGROUND
  Signaling events after activation of toll-like receptors (TLRs) are important mechanisms promoting inflammation in the atherosclerotic plaque. INF regulatory factor 5 (IRF5) is one of the mediators of downstream effects of TLRs. Several single nucleotide polymorphisms (SNPs) in the IRF5 gene have been found to be associated with systemic lupus erythematosus.
  
  
  RESULTS
  We examined IRF5 mRNA expression in carotid atherosclerotic tissue (n=99) and the case-control association between SNPs in the IRF5 gene with myocardial infarction (MI) (n=376+387) and unstable coronary artery disease (CAD) (n=3101+445). Among unstable CAD patients, association of IRF5 SNPs with recurrent coronary events (n=401) was also investigated. The IRF5 mRNA expression was increased in atherosclerotic tissue compared with control tissue (P<0.001). Significant associations with IRF5 expression was observed for 6 of 10 SNPs in the study. However, the IRF5 SNPs examined were neither associated with the risk of precocious MI, nor with unstable CAD or risk of recurrent cardiovascular events in unstable CAD patients.
  
  
  CONCLUSIONS
  IRF5 mRNA is expressed in cells in atherosclerotic tissue and its expression is modified by SNPs in the IRF5 gene. Genetic variation at the IRF5 locus was, however, not associated with CAD or related phenotypes.
authors.affiliation: Atherosclerosis Research Unit, Karolinska Institute, Stockholm, Sweden. anders.malarstig@ki.se
authors.forename: Anders
authors.initials: A
authors.lastname: Mälarstig
authors.forename: Snaevar
authors.initials: S
authors.lastname: Sigurdsson
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Paulsson-Berne
authors.forename: Ulf
authors.initials: U
authors.lastname: Hedin
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D012333:RNA, Messenger; D002097:C-Reactive Protein