title: Subtype specific genetic associations for juvenile idiopathic arthritis: ERAP1 with the enthesitis related arthritis subtype and IL23R with juvenile psoriatic arthritis.
abstract: BACKGROUND
  Juvenile idiopathic arthritis (JIA) is an umbrella term for all chronic childhood arthropathies and can be divided into seven subtypes. It includes the enthesitis related arthritis (ERA) subtype which displays symptoms similar to ankylosing spondylitis (AS) and juvenile-onset psoriatic arthritis which has similarities to psoriatic arthritis (PsA) and psoriasis (Ps). We, therefore, hypothesized that two well-established susceptibility loci for AS and Ps, ERAP1 and IL23R, could also confer susceptibility to these JIA subtypes.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in ERAP1 (rs30187) and IL23R (rs11209026) were genotyped in JIA cases (n = 1,054) and healthy controls (n = 5,200). Genotype frequencies were compared between all JIA cases and controls using the Cochrane-Armitage trend test implemented in PLINK. Stratified analysis by ILAR subtype was performed.
  
  
  RESULTS
  The ERA subtype showed strong association with ERAP1 SNP (P trend = 0.005). The IL23R SNP showed significant association in the PsA subtype (P trend = 0.04). The SNPs were not associated with JIA overall or with any other subtype.
  
  
  CONCLUSIONS
  We present evidence for subtype specific association of the ERAP1 gene with ERA JIA and the IL23R gene with juvenile-onset PsA. The findings will require validation in independent JIA datasets. These results suggest distinct pathogenic pathways in these subtypes.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, The University of Manchester, Manchester M139PT, UK. a.m.hinks@manchester.ac.uk
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Edward
authors.initials: E
authors.lastname: Flynn
authors.forename: Steve
authors.initials: S
authors.lastname: Eyre
authors.forename: Jon
authors.initials: J
authors.lastname: Packham
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
mesh_terms: D000626:Aminopeptidases / Q000235:genetics*; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000473:pathology; D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*
chemical_list: C515500:IL23R protein, human; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin; D000626:Aminopeptidases; C464841:ERAP1 protein, human