title: Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis.
abstract: OBJECTIVE
  Inflammasomes are intracellular protein complexes important for the production of pro-inflammatory 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.
  
  
  CONCLUSIONS
  Genetic variants of the NLRP3 inflammasome influence the risk of stroke/TIA, but not of MI/angina pectoris in Swedish patients with established RA.
authors.affiliation: From the Department of Rheumatology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping; the Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.A. Kastbom, MD, PhD, Department of Rheumatology, and Department of Clinical and Experimental Medicine, Linköping University; L. Ärlestig, PhD; S. Rantapää-Dahlqvist, Department of Public Health and Clinical Medicine/Rheumatology, Umeå University. alf.kastbom@liu.se.
authors.forename: Alf
authors.initials: A
authors.lastname: Kastbom
authors.affiliation: From the Department of Rheumatology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping; the Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.A. Kastbom, MD, PhD, Department of Rheumatology, and Department of Clinical and Experimental Medicine, Linköping University; L. Ärlestig, PhD; S. Rantapää-Dahlqvist, Department of Public Health and Clinical Medicine/Rheumatology, Umeå University.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Ärlestig
authors.affiliation: From the Department of Rheumatology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping; the Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.A. Kastbom, MD, PhD, Department of Rheumatology, and Department of Clinical and Experimental Medicine, Linköping University; L. Ärlestig, PhD; S. Rantapää-Dahlqvist, Department of Public Health and Clinical Medicine/Rheumatology, Umeå University.
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
mesh_terms: D017677:Age Distribution; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D015897:Comorbidity; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D058847:Inflammasomes / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D017678:Sex Distribution; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D013548:Sweden / Q000453:epidemiology
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: CARDIOVASCULAR DISEASE; GENETICS; INFLAMMASOMES; RHEUMATOID ARTHRITIS