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Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
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
Abstract [en]

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 >= 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 < 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
2015. Vol. 42, no 10, 1740-1745 p.
Keyword [en]
rheumatoid arthritis, inflammasomes, genetics, cardiovascular disease
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-111003DOI: 10.3899/jrheum.141529ISI: 000362234900004PubMedID: 26178285OAI: oai:DiVA.org:umu-111003DiVA: diva2:871806
Available from: 2015-11-17 Created: 2015-11-02 Last updated: 2016-02-04Bibliographically approved

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Ärlestig, LisbethRantapää-Dahlqvist, Solbritt
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