A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities.
Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis (odds ratio = 2.15, P = 0.00000085). This polymorphism alters the binding affinity of nuclear factor-kappaB and regulates FCRL3 expression. We observed high FCRL3 expression on B cells and augmented autoantibody production in individuals with the disease-susceptible genotype. We also found associations between the SNP and susceptibility to autoimmune thyroid disease and systemic lupus erythematosus. FCRL3 may therefore have a pivotal role in autoimmunity.
Kochi
Yuta
Y
Laboratory for Rheumatic Diseases, SNP Research Center, RIKEN, Yokohama 230-0045, Japan.
Yamada
Ryo
R
Suzuki
Akari
A
Harley
John B
JB
Shirasawa
Senji
S
Sawada
Tetsuji
T
Bae
Sang-Cheol
SC
Tokuhiro
Shinya
S
Chang
Xiaotian
X
Sekine
Akihiro
A
Takahashi
Atsushi
A
Tsunoda
Tatsuhiko
T
Ohnishi
Yozo
Y
Kaufman
Kenneth M
KM
Kang
Changsoo Paul
CP
Kang
Changwon
C
Otsubo
Shigeru
S
Yumura
Wako
W
Mimori
Akio
A
Koike
Takao
T
Nakamura
Yusuke
Y
Sasazuki
Takehiko
T
Yamamoto
Kazuhiko
K
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D005786:Gene Expression Regulation / Q000502:physiology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism
C457775:FCRL3 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D011971:Receptors, Immunologic