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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:975.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Variants of the Interferon Regulatory Factor 5 Gene Regulate Expression of IRF5 mRNA in Atherosclerotic Tissue But Are Not Associated With Myocardial Infarction

Anders Mälarstig; Snaevar Sigurdsson; Per Eriksson; Gabrielle Paulsson-Berne; Ulf Hedin; Lars Wallentin; Agneta Siegbahn; Anders Hamsten; Ann-Christine Syvänen

From the Atherosclerosis Research Unit (A.M., P.E., A.H.) and Experimental Cardiovascular Unit (G.P.-B.), Department of Medicine-Solna, and Vascular Surgery Unit (U.H.), Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm; and Molecular Medicine (S.S., A.-C.S.), Clinical Chemistry (A.S.), and Cardiology (L.W.), Department of Medical Sciences, Uppsala University, Sweden.

Correspondence to Anders Mälarstig, Building L8:03, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. E-mail anders.malarstig{at}ki.se

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.

Key Words: acute coronary syndromes • pathophysiology • gene regulation • genetics of cardiovascular disease • arterial thrombosis