A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis

Ann Rheum Dis. 2010 Aug;69(8):1471-4. doi: 10.1136/ard.2009.114934. Epub 2009 Sep 3.


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).

Conclusion: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / genetics
  • Adolescent
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology
  • Arthritis, Rheumatoid / genetics*
  • Autoantibodies / analysis*
  • Autoimmune Diseases / genetics
  • Child
  • Diabetes Mellitus, Type 1 / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Lectins, C-Type / genetics*
  • Monosaccharide Transport Proteins / genetics*
  • Peptides, Cyclic / immunology*
  • Polymorphism, Single Nucleotide


  • Autoantibodies
  • CLEC16A protein, human
  • Lectins, C-Type
  • Monosaccharide Transport Proteins
  • Peptides, Cyclic
  • cyclic citrullinated peptide