title: Autoinflammatory gene polymorphisms and susceptibility to UK juvenile idiopathic arthritis.
abstract: BACKGROUND
  To investigate the autoinflammatory hereditary periodic fever syndrome genes MVK and TNFRSF1A, and the NLRP1 and IL1 genes, for association with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  For MVK, TNFRSF1A and NLRP1 pair-wise tagging SNPs across each gene were selected and for IL1A SNPs from a prior meta-analysis were included. 1054 UK Caucasian JIA patients were genotyped by Sequenom iPlex MassARRAY and allele and genotype frequencies compared with 5380 unrelated healthy UK Caucasian controls.
  
  
  RESULTS
  Four SNPs were significantly associated with UK JIA: rs2071374 within intron 4 of IL1A (ptrend=0.006), rs2228576 3' of TNFRSF1A (ptrend=0.009) and 2 SNPs, rs11836136 and rs7957619, within MVK (ptrend=0.006, ptrend=0.005 respectively). In all cases the association appeared to be driven by the systemic-onset JIA (SoJIA) subtype. Genotype data for the two MVK SNPs was available in a validation cohort of 814 JIA (oligoarticular and RF negative polyarticular) cases and 3058 controls from the US. Replication was not confirmed, however, further suggesting that this association is specific to SoJIA.
  
  
  CONCLUSIONS
  These findings extend the observations of the relevance of studying monogenic loci as candidates for complex diseases. We provide novel evidence of association of MVK and TNFRSF1A with UK JIA, specifically driven by association with SoJIA and further confirm that the IL1A SNP association with SoJIA is subtype specific. Replication is required in independent cohorts.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Stopford Building, The University of Manchester, Manchester Academic Health Science Centre, School of Translational Medicine, Oxford Road, Manchester M13 9PT, UK. Rachelle.donn@manchester.ac.uk.
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Marc
authors.initials: M
authors.lastname: Sudman
authors.forename: Carmel J
authors.initials: CJ
authors.lastname: Stock
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Day
authors.forename: Jon
authors.initials: J
authors.lastname: Packham
authors.forename: Athimalaipet V
authors.initials: AV
authors.lastname: Ramanan
authors.forename: Rachelle P
authors.initials: RP
authors.lastname: Donn
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