Variants of the interferon regulatory factor 5 gene regulate expression of IRF5 mRNA in atherosclerotic tissue but are not associated with myocardial infarction.
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.
Mälarstig
Anders
A
Atherosclerosis Research Unit, Karolinska Institute, Stockholm, Sweden. anders.malarstig@ki.se
Sigurdsson
Snaevar
S
Eriksson
Per
P
Paulsson-Berne
Gabrielle
G
Hedin
Ulf
U
Wallentin
Lars
L
Siegbahn
Agneta
A
Hamsten
Anders
A
Syvänen
Ann-Christine
AC
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
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D012333:RNA, Messenger; D002097:C-Reactive Protein