TY - JOUR
T1 - Interferon regulatory factor 5 gene variants rs2004640 and rs4728142 are associated with carotid intima media thickness but not with cardiovascular events in rheumatoid arthritis
AU - Agca, Rabia
AU - van Sijl, Alper M.
AU - Vosslamber, Saskia
AU - Voskuyl, Alexandre E.
AU - Verweij, Cor L.
AU - Nurmohamed, Michael T.
N1 - geen DOI Funding Information: Funding: this research was partly funded by the European Community Sixth Framework Programmes Autorome (from Immune Responses in Rare Auto immune Diseases to Novel Therapeutic Intervention Strategies - a Personalized Medicine Approach) and Autocure (Curing Autoimmune Diseases) and the Dutch Centre for Medical System Biology (CMSB). These sponsors had no involvement in the study design, analysis or interpretation of the data and publication. Competing interests: none declared. Funding Information: this research was partly funded by the European Community Sixth Framework Programmes Autorome (from Immune Responses in Rare Autoimmune Diseases to Novel Therapeutic Intervention Strategies - a Personalized Medicine Approach) and Autocure (Curing Autoimmune Diseases) and the Dutch Centre for Medical System Biology (CMSB). These sponsors had no involvement in the study design, analysis or interpretation of the data and publication. Publisher Copyright: © Copyright Clinical and Experimental Rheumatology 2022.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Objective: Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality. Interferon regulatory factor 5 (IRF5) gene polymorphisms rs2004640 and rs4728142 have been associated with autoimmune diseases, but also with atherosclerosis. Differences in IRF5 gene expression can lead to the production of different interferons and might play a role in the atherogenic process in RA. Methods: We investigated the effects of IRF5 gene variants rs2004640 and rs4728142 on clinical parameters related to atherosclerosis, such as cIMT (in subgroup n=101), and new CV events (in whole cohort n=353). Results: For rs2004640, cIMT values at baseline were highest within the group of patients carrying the GG-genotype, followed by GT- and TT- genotypes, which was statistically significant. Over time patients with the TT-genotype had the highest increase in cIMT. For rs4728142 cIMT values were also the highest for patients with the GG-genotype at baseline, but the difference between the groups was not statistically significant. Over time the highest increase in cIMT was in the patients with the AA-genotype. Both rs2004640 and rs4728142 were not associated with new CV events during follow-up. Conclusion: IRF5 alleles are associated with changes in cIMT, but not with new CV events in RA. Although these findings implicate a role of the IRF5 transcription pathway in atherosclerosis, IRF5 single nucleotide polymorphisms do not appear to increase the risk of future CV events.
AB - Objective: Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality. Interferon regulatory factor 5 (IRF5) gene polymorphisms rs2004640 and rs4728142 have been associated with autoimmune diseases, but also with atherosclerosis. Differences in IRF5 gene expression can lead to the production of different interferons and might play a role in the atherogenic process in RA. Methods: We investigated the effects of IRF5 gene variants rs2004640 and rs4728142 on clinical parameters related to atherosclerosis, such as cIMT (in subgroup n=101), and new CV events (in whole cohort n=353). Results: For rs2004640, cIMT values at baseline were highest within the group of patients carrying the GG-genotype, followed by GT- and TT- genotypes, which was statistically significant. Over time patients with the TT-genotype had the highest increase in cIMT. For rs4728142 cIMT values were also the highest for patients with the GG-genotype at baseline, but the difference between the groups was not statistically significant. Over time the highest increase in cIMT was in the patients with the AA-genotype. Both rs2004640 and rs4728142 were not associated with new CV events during follow-up. Conclusion: IRF5 alleles are associated with changes in cIMT, but not with new CV events in RA. Although these findings implicate a role of the IRF5 transcription pathway in atherosclerosis, IRF5 single nucleotide polymorphisms do not appear to increase the risk of future CV events.
KW - Arthritis, Rheumatoid/diagnosis
KW - Cardiovascular Diseases/epidemiology
KW - Cardiovascular disease
KW - Carotid Intima-Media Thickness
KW - Genetic Predisposition to Disease
KW - Humans
KW - Interferon Regulatory Factors/genetics
KW - Interferon regulatory factor 5
KW - Polymorphism, Single Nucleotide
KW - Rheumatoid arthritis
KW - Risk Factors
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85123879555&partnerID=8YFLogxK
U2 - https://doi.org/10.55563/clinexprheumatol/pf511x
DO - https://doi.org/10.55563/clinexprheumatol/pf511x
M3 - Article
C2 - 33666161
SN - 0392-856X
VL - 40
SP - 64
EP - 68
JO - Clinical and experimental rheumatology
JF - Clinical and experimental rheumatology
IS - 1
ER -