A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis.
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.
Skinningsrud
Beate
B
Department of Medical Genetics, Oslo University Hospital, Ullevål, Kirkeveien 166, N-0407 Oslo, Norway. beate.skinningsrud@medisin.uio.no
Lie
Benedicte A
BA
Husebye
Eystein S
ES
Kvien
Tore K
TK
Førre
Øystein
Ø
Flatø
Berit
B
Stormyr
Alice
A
Joner
Geir
G
Njølstad
Pål R
PR
Egeland
Thore
T
Undlien
Dag E
DE
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
D001323:Autoantibodies; C522505:CLEC16A protein, human; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide