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.
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: Anusha N Seneviratne; Andreas Edsfeldt; Jennifer E Cole; Christina Kassiteridi; Maarten Swart; Inhye Park; Patricia Green; Tariq Khoyratty; David Saliba; Michael E Goddard; Stephen N Sansom; Isabel Goncalves; Rob Krams; Irina A Udalova; Claudia Monaco Journal: Circulation Date: 2017-07-11 Impact factor: 29.690
Authors: Leah C Kottyan; Erin E Zoller; Jessica Bene; Xiaoming Lu; Jennifer A Kelly; Andrew M Rupert; Christopher J Lessard; Samuel E Vaughn; Miranda Marion; Matthew T Weirauch; Bahram Namjou; Adam Adler; Astrid Rasmussen; Stuart Glenn; Courtney G Montgomery; Gideon M Hirschfield; Gang Xie; Catalina Coltescu; Chris Amos; He Li; John A Ice; Swapan K Nath; Xavier Mariette; Simon Bowman; Maureen Rischmueller; Sue Lester; Johan G Brun; Lasse G Gøransson; Erna Harboe; Roald Omdal; Deborah S Cunninghame-Graham; Tim Vyse; Corinne Miceli-Richard; Michael T Brennan; James A Lessard; Marie Wahren-Herlenius; Marika Kvarnström; Gabor G Illei; Torsten Witte; Roland Jonsson; Per Eriksson; Gunnel Nordmark; Wan-Fai Ng; Juan-Manuel Anaya; Nelson L Rhodus; Barbara M Segal; Joan T Merrill; Judith A James; Joel M Guthridge; R Hal Scofield; Marta Alarcon-Riquelme; Sang-Cheol Bae; Susan A Boackle; Lindsey A Criswell; Gary Gilkeson; Diane L Kamen; Chaim O Jacob; Robert Kimberly; Elizabeth Brown; Jeffrey Edberg; Graciela S Alarcón; John D Reveille; Luis M Vilá; Michelle Petri; Rosalind Ramsey-Goldman; Barry I Freedman; Timothy Niewold; Anne M Stevens; Betty P Tsao; Jun Ying; Maureen D Mayes; Olga Y Gorlova; Ward Wakeland; Timothy Radstake; Ezequiel Martin; Javier Martin; Katherine Siminovitch; Kathy L Moser Sivils; Patrick M Gaffney; Carl D Langefeld; John B Harley; Kenneth M Kaufman Journal: Hum Mol Genet Date: 2014-09-08 Impact factor: 6.150