Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus

• Published in: Lupus Vol. 22; no. 5; pp. 497 - 503
• Main Authors: Furukawa, H, Kawasaki, A, Oka, S, Shimada, K, Matsui, T, Ikenaka, T, Hashimoto, A, Okazaki, Y, Takaoka, H, Futami, H, Komiya, A, Kondo, Y, Ito, S, Hayashi, T, Matsumoto, I, Kusaoi, M, Takasaki, Y, Nagai, T, Hirohata, S, Setoguchi, K, Suda, A, Nagaoka, S, Kono, H, Okamoto, A, Chiba, N, Suematsu, E, Fukui, N, Hashimoto, H, Sumida, T, Ono, M, Tsuchiya, N, Tohma, S
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.04.2013; Sage Publications Ltd
• Subjects: Adult; Asian Continental Ancestry Group; Case-Control Studies; Female; Genes; Genetic Predisposition to Disease; Hospitals; Humans; Infectious diseases; Internal medicine; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Introns; Japan; Jurkat Cells; Kinases; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Luciferases; Lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - metabolism; Medicine; Middle Aged; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Rheumatology; Signaling Lymphocytic Activation Molecule Associated Protein; X chromosomes; Japan; SLAM-associated protein; Systemic lupus erythematosus; medical genetics; single nucleotide polymorphism; SH2D1A
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203313479421

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.