The FCRL3 -169T>C polymorphism is associated with rheumatoid arthritis and shows suggestive evidence of involvement with juvenile idiopathic arthritis in a Scandinavian panel of autoimmune diseases.
OBJECTIVE
The Fc receptor-like 3 (FCRL3) gene -169T>C single nucleotide polymorphism (SNP) has been reported to be associated with several autoimmune diseases (AIDs) in Japanese populations. However, association results in other populations have been conflicting. Therefore, we investigated this SNP in a Scandinavian panel of AIDs.


METHODS
We genotyped patients with rheumatoid arthritis (RA; n = 708), juvenile idiopathic arthritis (JIA; n = 524), systemic lupus erythaematosus (SLE; n = 166), ulcerative colitis (UC; n = 335), primary sclerosing cholangitis (PSC; n = 365), Crohn disease (CD; n = 149), a healthy control group (n = 1030) and 425 trio families with type 1 diabetes (T1D). Statistical analysis consisted of case-control and family-based association tests.


RESULTS
RA was associated with the C allele (odds ratio (OR) = 1.16, 95% CI 1.01 to 1.33) and the CC genotype (OR = 1.30, 95% CI 1.01 to 1.67) of the FCRL3 -169T>C SNP in our material. Suggestive evidence for association was also found for JIA (CC genotype: OR = 1.30, 95% CI 0.99 to 1.70), and clinical subgroup analysis indicated that this was connected to the polyarticular subgroup. No significant association was found with SLE, UC, CD, PSC or T1D. In patients with RA, we found no significant interaction between the FCRL3 -169T>C and PTPN22 1858C>T SNPs, nor between the FCRL3 -169CC genotype and IgM-rheumatoid factor or anti-cyclic citrullinated peptide titre levels.


CONCLUSIONS
We found an association between the FCRL3 -169T>C SNP and RA, and suggestive evidence for involvement with JIA, in a Norwegian population. These findings lend support for a role for this SNP in RA across ethnically diverse populations, and warrant follow-up studies in JIA.
Institute of Immunology, Rikshospitalet HF, N-0027 Oslo, Norway. Morten.Eike@rr-research.no
M C
MC
Eike
G B N
GB
Nordang
T H
TH
Karlsen
K M
KM
Boberg
M H
MH
Vatn
K
K
Dahl-Jørgensen
K S
KS
Rønningen
G
G
Joner
B
B
Flatø
A
A
Bergquist
E
E
Thorsby
O
O
Førre
T K
TK
Kvien
D E
DE
Undlien
B A
BA
Lie
D001171:Arthritis, Juvenile / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*
C457775:FCRL3 protein, human; D011971:Receptors, Immunologic