title: Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population.
abstract: 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.
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamatani
authors.forename: Mikako
authors.initials: M
authors.lastname: Mori
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimane
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyatake
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: 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
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family