Background and Objectives Rheumatoid arthritis (RA) is a chronic inflammatory joint disease and is associated with an increased cardiovascular (CV) risk. Interferons (IFNs), especially IFNβ, might play a role in atherosclerosis as they are known inhibitors of vascular smooth muscle cell proliferation and intimal hyperplasia. We studied whether functional relevant SNPs in the interferon regulatory factor 5 (IRF5) gene are associated with carotid intima media thickness (cIMT), a surrogate maker for CV disease.
Materials and Methods In 353 RA patients of the CARRÉ study, IRF5 SNPs rs2004640 and rs4728142 were determined using Taqman Genotyping assay. cIMT was determined in a subgroup of 101 patients by B-mode ultrasonography. Linear regression analyses were used to investigate the association between cIMT and IRF5 genotypes, adjusting for demographic and cardiovascular risk factors.
Results Patients homozygous for rs2004640 G-allele have higher cIMT compared to those homozygote for the T-allele (p = 0.019) and a trend towards a higher cIMT was observed (p = 0.103) for patients homozygous for the rs4728142 G-allele versus patients with the AA-genotype. Age was an effect-modifier for this association. Linear regression analysis in patients older than 60 years showed that the rs2004640 GG-genotype was associated with higher cIMT (regression coefficient 0.107 (C. I. 0.008; 0.205), p = 0.035) compared to the TT-genotype. This remained significant after adjustment for traditional risk factors (regression coefficient 0.111 (C. I.0.02; 0.202), p = 0.020).
Conclusion We demonstrate that the IRF5 gene variant rs2004640 is associated with preclinical atherosclerosis in RA patients, independent of traditional cardiovascular risk factors. These results might implicate a role for type I IFN in modulating CV disease features in RA.