Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis
2015 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 10, 1740-1745 p.Article in journal (Refereed) Published
Objective. Inflammasomes are intracellular protein complexes important for the production of proinflammatory cytokines. Studies have suggested that the NLRP3 inflammasome influences both the severity of rheumatoid arthritis (RA) and development of atherosclerosis. Therefore, we investigated whether functional genetic variants related to the NLRP3 inflammasome influence the risk of cardiovascular (CV) disease (CVD) in patients with RA. Methods. The incidence of CVD was assessed in 522 patients with established RA by a retrospective survey of medical records in combination with a 6-year prospective followup. NLRP3-Q705K and CARD8-C10X genotypes were analyzed in relation to CVD by logistic regression, adjusting for traditional risk factors, antirheumatic treatment, and age at the onset of RA. Results. Carriage of the NLRP3-Q705K minor allele was associated with an increased risk of stroke/transient ischemic attack (TIA; OR 2.01, 95% CI 1.0-4.1, p = 0.05), while CARD8-C10X was not associated with any type of CV event. Patients with greater than= 1 variant allele in both polymorphisms had an increased risk of CVD when compared with patients without variant alleles present in both polymorphisms (adjusted OR 3.05, 95% CI 1.42-6.54, p = 0.004). Stratification showed that this risk was confined to stroke/TIA (adjusted OR 5.09, 95% CI 2.27-11.44, p less than 0.0001) and not to myocardial infarction (MI)/angina pectoris (adjusted OR 1.58, 95% CI 0.67-3.73). Risk estimates were consistently higher among female patients. Conclusion. Genetic variants of the NLRP3 inflammasome influence the risk of stroke/TIA, but not of MI/angina pectoris in Swedish patients with established RA.
Place, publisher, year, edition, pages
J RHEUMATOL PUBL CO , 2015. Vol. 42, no 10, 1740-1745 p.
RHEUMATOID ARTHRITIS; INFLAMMASOMES; GENETICS; CARDIOVASCULAR DISEASE
IdentifiersURN: urn:nbn:se:liu:diva-122433DOI: 10.3899/jrheum.141529ISI: 000362234900004PubMedID: 26178285OAI: oai:DiVA.org:liu-122433DiVA: diva2:866762
Funding Agencies|County Council of Ostergotland; Reinhold Sund Foundation; Swedish Society of Medicine; Swedish Research Council [K2011-68X-20611-04-3, Dnr 825-2010-5986]; King Gustaf Vs 80-Year Fund; King Gustaf Vs and Queen Victorias Fund; Swedish Rheumatism Association; Swedish COMBINE program; Vasterbotten county council; Swedish Foundation for Strategic Research2015-11-032015-11-022015-11-03