Autoinflammatory genes and susceptibility to psoriatic juvenile idiopathic arthritis

Arthritis Rheum. 2008 Jul;58(7):2142-6. doi: 10.1002/art.23604.


Objective: To investigate the association of NLRP3, NOD2, MEFV, and PSTPIP1, genes that cause 4 of the autoinflammatory hereditary periodic fever syndromes (HPFS), with juvenile idiopathic arthritis (JIA).

Methods: Fifty-one single-nucleotide polymorphisms (SNPs) across the 4 loci were investigated using MassArray genotyping in 950 Caucasian patients with JIA living in the UK and 728 ethnically matched healthy controls.

Results: Prior to Bonferroni correction for multiple testing, significant genotype associations between 6 SNPs in MEFV and JIA were observed and, in subgroup analysis, associations between 12 SNPs across all 4 loci and the subgroup of patients with psoriatic JIA were found. After Bonferroni correction for multiple testing, 2 genotype associations remained significant in the subgroup of patients with psoriatic JIA (MEFV SNP rs224204 [corrected P = 0.025] and NLRP3 SNP rs3806265 [corrected P = 0.04]).

Conclusion: These findings support the use of monogenic loci as candidates for investigating the genetic component of complex disease and provide preliminary evidence of association between SNPs in autoinflammatory genes and psoriatic JIA. Our findings raise the interesting possibility of a shared disease mechanism between the HPFS and psoriatic JIA, potentially involving abnormal production of interleukin-1beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Arthritis, Juvenile / genetics*
  • Arthritis, Psoriatic / genetics*
  • Carrier Proteins / genetics
  • Case-Control Studies
  • Cytoskeletal Proteins / genetics
  • Familial Mediterranean Fever / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nod2 Signaling Adaptor Protein / genetics
  • Polymorphism, Single Nucleotide
  • Pyrin
  • United Kingdom


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • MEFV protein, human
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • PSTPIP1 protein, human
  • Pyrin