title: NLRP3andCARD8Polymorphisms Influence Higher Disease Activity in Rheumatoid Arthritis.
abstract: BACKGROUND
  The activation of NLRP3-inflammasome may contribute to inflammatory processes in rheumatoid arthritis (RA). Functional polymorphisms in the genes coding for its components NLRP3 and CARD8 were associated with a proinflammatory phenotype. Our aim was to investigate the influence of these polymorphisms on RA susceptibility and disease activity at the time of diagnosis and after six months of treatment.
  
  
  METHODS
  A group of 128 RA patients treated with methotrexate and 122 healthy controls were genotyped forNLRP3rs35829419 (p. Q705K) andCARD8rs2043211 (p. C10X) polymorphisms.
  
  
  RESULTS
  RA susceptibility was not influenced by the investigated polymorphisms or their interaction. The investigated polymorphisms explained 8% of variability in DAS28 at the time of diagnosis. Carriers ofNLRP3rs35829419 orCARD8rs2043211 polymorphisms had significantly higher DAS28 at the time of diagnosis (p=0.003; p=0.022; respectively). PolymorphicCARD8rs2043211 TT genotype was also associated with higher DAS28 after six months of treatment (p=0.033).
  
  
  CONCLUSIONS
  Genetic variability of inflammasome components may contribute to higher disease activity at the time of diagnosis and after 6 months of methotrexate treatment in RA patients. Better understanding of the immunological mechanisms behind a more active course of RA may suggest novel treatment approaches in a subset of patients with a proinflammatory phenotype.
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jenko
authors.affiliation: Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Praprotnik
authors.affiliation: Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Matija
authors.initials: M
authors.lastname: Tomšic
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Vita
authors.initials: V
authors.lastname: Dolžan
keywords: BIRC5; NLRP3; inflammasome; polymorphism; rheumatoid arthritis