title: Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus.
abstract: SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Japan. h-furukawa@sagamihara-hosp.gr.jp
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
authors.forename: A
authors.initials: A
authors.lastname: Kawasaki
authors.forename: S
authors.initials: S
authors.lastname: Oka
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: T
authors.initials: T
authors.lastname: Ikenaka
authors.forename: A
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Okazaki
authors.forename: H
authors.initials: H
authors.lastname: Takaoka
authors.forename: H
authors.initials: H
authors.lastname: Futami
authors.forename: A
authors.initials: A
authors.lastname: Komiya
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: I
authors.initials: I
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Kusaoi
authors.forename: Y
authors.initials: Y
authors.lastname: Takasaki
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: S
authors.initials: S
authors.lastname: Hirohata
authors.forename: K
authors.initials: K
authors.lastname: Setoguchi
authors.forename: A
authors.initials: A
authors.lastname: Suda
authors.forename: S
authors.initials: S
authors.lastname: Nagaoka
authors.forename: H
authors.initials: H
authors.lastname: Kono
authors.forename: A
authors.initials: A
authors.lastname: Okamoto
authors.forename: N
authors.initials: N
authors.lastname: Chiba
authors.forename: E
authors.initials: E
authors.lastname: Suematsu
authors.forename: N
authors.initials: N
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Sumida
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: N
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: S
authors.initials: S
authors.lastname: Tohma
mesh_terms: D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D007564:Japan; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008156:Luciferases; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D008156:Luciferases