title: Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic arthritis in a Taiwanese population.
abstract: OBJECTIVE
  An elevated interleukin (IL)-1β response in peripheral blood mononuclear cells (PBMCs) has been observed in systemic juvenile idiopathic arthritis (sJIA), suggesting a role for inflammasomes in the pathogenesis of JIA. We aimed to determine whether genetic polymorphisms of the NLRP3 inflammasome components confer risk for oligoarticular and polyarticular JIA in a Taiwanese population.
  
  
  METHODS
  A total of 118 JIA patients and 103 healthy controls were genotyped for rs4353135 OR2B11/NLRP3 and rs2043211 CARD8 polymorphisms. Clinical laboratory data and serum IL-1β of JIA patients were evaluated by medical chart review and enzyme-linked immunosorbent assay (ELISA), respectively. The production of IL-17 in lymphocytes of different genotype carriers was measured using flow cytometry.
  
  
  RESULTS
  The variant rs4353135 G allele carrier conferred increased risk for oligoarticular and polyarticular JIA. The G allele was also found to be associated with higher levels of clinical inflammatory markers. Moreover, G variant carriers enhanced the lymphocyte IL-17 response. The G/G genotype further increased the need for treatment with the tumour necrosis factor (TNF) inhibitor etanercept.
  
  
  CONCLUSIONS
  Our data indicate that the rs4353135 OR2B11/NLRP3 polymorphism might be functional in, and could contribute to, the pathophysiology of oligoarticular and polyarticular JIA in a Taiwanese population.
authors.affiliation: Departments of Paediatrics, National Taiwan University Hospital , Taipei , Taiwan.
authors.forename: C-A
authors.initials: CA
authors.lastname: Yang
authors.forename: S-T
authors.initials: ST
authors.lastname: Huang
authors.forename: B-L
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000068800:Etanercept; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D058847:Inflammasomes / Q000502:physiology; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013624:Taiwan / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D002352:Carrier Proteins; D007074:Immunoglobulin G; D058847:Inflammasomes; D020381:Interleukin-17; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept