Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population.
Rheumatoid arthritis is a chronic autoimmune inflammatory disease with a complex genetic etiology. Members of the signaling lymphocyte activation molecule (SLAM) family carry out pivotal functions in innate immunity and in conventional lymphocytes. We identified a linkage disequilibrium block associated with rheumatoid arthritis in the chromosome 1q region containing multiple SLAM family genes. In this block, the association peaked at two functional SNPs (rs3766379 and rs6682654) in CD244 in two independent rheumatoid arthritis cohorts from Japan (P = 3.23 x 10(-8) and P = 7.45 x 10(-8)). We also identified a Japanese cohort with systemic lupus erythematosus that had a similar genotype distribution as the rheumatoid arthritis cohorts. We demonstrated that the rheumatoid arthritis-susceptible alleles of rs3766379 and rs6682654 and their haplotype increased their expression in luciferase and allele-specific transcript quantification assays. CD244 is a genetic risk factor for rheumatoid arthritis and may have a role in the autoimmune process shared by rheumatoid arthritis and systemic lupus erythematosus.
Suzuki
Akari
A
Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
Yamada
Ryo
R
Kochi
Yuta
Y
Sawada
Tetsuji
T
Okada
Yukinori
Y
Matsuda
Koichi
K
Kamatani
Yoichiro
Y
Mori
Mikako
M
Shimane
Kenichi
K
Hirabayashi
Yasuhiko
Y
Takahashi
Atsushi
A
Tsunoda
Tatsuhiko
T
Miyatake
Akihiko
A
Kubo
Michiaki
M
Kamatani
Naoyuki
N
Nakamura
Yusuke
Y
Yamamoto
Kazuhiko
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D015331:Cohort Studies; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; C084093:CD244 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family