Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project)
2008 (English)In: Rheumatology, ISSN 1462-0332 (online) 1462-0324 (print), Vol. 47, no 4, 415-417 p.Article in journal (Refereed) Published
Objectives: The genetic background to RA is incompletely understood.As new cytokine-targeted therapies emerge, early predictorsof disease severity are becoming increasingly important. Theinflammasomes are essential regulators of cytokine production.We investigated whether two polymorphisms in the genes encodingcryopyrin (CIAS1) and TUCAN (CARD8) influence susceptibilityand disease course in RA.
Methods: Genotype frequencies were assessed in 174 Swedish patientswith early RA and 360 population-based controls without rheumaticdisease. Genotypes were categorized according to the presence(+) or absence (–) of two wild-type alleles and comparedbetween patients and controls. In the RA patients, antibodiestowards cyclic citrullinated peptides (anti-CCP) and the ‘sharedepitope’ (SE) were assessed, and medication and measuresof disease activity were monitored regularly during 3 yrs.
Results: The combination of CIAS1/TUCAN –/–, ascompared with CIAS1/TUCAN +/+, was significantly more commonamong patients than in controls [odds ratio (OR) 2.2, 95% CI1.03–4.6]. This association was strengthened when patientswere divided into anti-CCP+ [OR 2.8 (1.1–6.7)] or presenceof 1 SE copy [OR 2.8 (1.3–6.2)]. At most time-points duringthe 3-yr follow-up, patients with CIAS1/TUCAN –/–showed significantly higher disease activity. Furthermore, CIAS1/TUCAN–/– patients proved to be much more likely to receiveTNF-blocking therapy [relative risk 20 (2.6–149)].
Conclusions: Compound polymorphisms in CIAS1 and TUCAN associatewith RA susceptibility and severity. The cryopyrin inflammasomeneeds further attention regarding a possible aetiopathogeneticconnection with RA.
Place, publisher, year, edition, pages
2008. Vol. 47, no 4, 415-417 p.
Disease course, Genetics, Inflammasome, Rheumatoid arthritis
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-14380DOI: 10.1093/rheumatology/kem372OAI: oai:DiVA.org:liu-14380DiVA: diva2:23362