title: A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis.
abstract: OBJECTIVE
  Variants in CLEC16A have conferred susceptibility to autoimmune diseases in genome-wide association studies. The present work aimed to investigate the locus' involvements in juvenile idiopathic arthritis (JIA) and further explore the association with rheumatoid arthritis (RA), type 1 diabetes (T1D) and Addison's disease (AD) in the Norwegian population.
  
  
  METHODS
  Three single nucleotide polymorphisms (SNPs) were genotyped in patients with RA (n=809), JIA (n=509), T1D (n=1211) and AD (n=414) and in healthy controls (n=2149).
  
  
  RESULTS
  All diseases were associated with CLEC16A, but with different SNPs. The intron 22 SNP, rs6498169, was associated with RA (p=0.006) and JIA (p=0.016) and the intron 19 SNPs, rs12708716/rs12917716, with T1D (p=1x10-5) and AD (p=2x10-4). The RA association was confined to the anti-cyclic citrullinated peptide antibody (anti-CCP) negative subgroup (p=2x10-4).
  
  
  CONCLUSIONS
  This is the first report of a CLEC16A association with JIA and a split of the RA association according to anti-CCP status. Different causative variants underlie the rheumatic versus the organ specific diseases.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Ullevål, Kirkeveien 166, N-0407 Oslo, Norway. beate.skinningsrud@medisin.uio.no
authors.forename: Beate
authors.initials: B
authors.lastname: Skinningsrud
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Førre
authors.forename: Berit
authors.initials: B
authors.lastname: Flatø
authors.forename: Alice
authors.initials: A
authors.lastname: Stormyr
authors.forename: Geir
authors.initials: G
authors.lastname: Joner
authors.forename: Pål R
authors.initials: PR
authors.lastname: Njølstad
authors.forename: Thore
authors.initials: T
authors.lastname: Egeland
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
mesh_terms: D000224:Addison Disease / Q000235:genetics; D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000235:genetics; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010456:Peptides, Cyclic / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D001323:Autoantibodies; C522505:CLEC16A protein, human; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide