Document Detail


Variants of the interferon regulatory factor 5 gene regulate expression of IRF5 mRNA in atherosclerotic tissue but are not associated with myocardial infarction.
MedLine Citation:
PMID:  18323517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. METHODS AND 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:
Anders Mälarstig; Snaevar Sigurdsson; Per Eriksson; Gabrielle Paulsson-Berne; Ulf Hedin; Lars Wallentin; Agneta Siegbahn; Anders Hamsten; Ann-Christine Syvänen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-06
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  28     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-18     Completed Date:  2008-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  975-82     Citation Subset:  IM    
Affiliation:
Atherosclerosis Research Unit, Karolinska Institute, Stockholm, Sweden. anders.malarstig@ki.se
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Angiography
Atherosclerosis / metabolism*,  pathology
C-Reactive Protein / metabolism
Carotid Arteries / metabolism,  pathology
Carotid Stenosis / metabolism*,  pathology
Case-Control Studies
Female
Genotype
Humans
Interferon Regulatory Factors / genetics,  metabolism*
Interleukin-6 / blood
Male
Middle Aged
Myocardial Infarction / metabolism*,  pathology
Polymorphism, Single Nucleotide / genetics
RNA, Messenger / genetics,  metabolism*
Severity of Illness Index
Chemical
Reg. No./Substance:
0/IRF5 protein, human; 0/Interferon Regulatory Factors; 0/Interleukin-6; 0/RNA, Messenger; 9007-41-4/C-Reactive Protein

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