The regulation of the expression of SH2D1A gene in systemic lupus erythematosus.

• Project/Area Number: 22591090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: FURUKAWA Hiroshi 独立行政法人国立病院機構(相模原病院臨床研究センター), 遺伝子診断・治療研究室, 室長 (00372293)
• Co-Investigator(Kenkyū-buntansha): TOUMA Shigeto 独立行政法人国立病院機構(相模原病院臨床研究センター), リウマチ性疾患研究部, 部長 (50207528)
• Co-Investigator(Renkei-kenkyūsha): TSUCHIYA Naoyuki 筑波大学, 医学医療系, 教授 (60231437)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膠原病学 / 疾患関連遺伝子 / 全身性エリテマトーデス / SAP / 遺伝解析 / SLE

Research Abstract

SH2D1A, also known as 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.

Research Products

• [Journal Article] A novel HLA-DQB1*04 allele, DQB1*04:10, identified in a Japanese individual. (2013)
  • Author(s): Oka S, Furukawa H, Kashiwase K, Tsuchiya N, Tohma S.
  • Journal Title: Tissue Antigens
• [Journal Article] Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis. (2013)
  • Author(s): Genin E, Coustet B, Allanore Y, Ito I, Teruel M, Constantin A, Schaeverbeke T, Ruyssens-Witran A, Tohma S, Cantagrel A, Vittecoq O, Barnetche T, Le Loet X, Fardellone P, Furukawa H, Meyer O, Chiocchia G, Tsuchiya N, Martin J, Dieude P.
  • Journal Title: PLoS One. Volume: 8(4)
• [Journal Article] Serum biomarker analysis of collagen disease patients with acute-onset diffuse interstitial lung disease (2013)
  • Author(s): Oka S, Furukawa H, Shimada K, Hayakawa H, Fukui N, Tsuchiya N, Tohma S.
  • Journal Title: BMC Immunology Volume: 14(1) Pages: 9-9
• [Journal Article] Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus. (2013)
  • Author(s): 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.
  • Journal Title: Lupus Volume: 22(5) Pages: 497-503
• [Journal Article] Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients. (2013)
  • Author(s): Furukawa H, Oka S, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Nagai T, Hirohata S, Setoguchi K, Okamoto A, Chiba N, Suematsu E, Miyashita T, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S.
  • Journal Title: PLoS One. Volume: 8(1)
• [Journal Article] Genome, epigenome and transcriptome analyses of a pair of monozygotic twins discordant for systemic lupus erythematosus. (2013)
  • Author(s): Furukawa H, Oka S, Matsui T, Hashimoto A, Arinuma Y, Komiya A, Fukui N, Tsuchiya N, Tohma S.
  • Journal Title: Hum Immunol. Volume: 74(2) Pages: 170-5
• [Journal Article] HLA-A*31:01 and methotrexate-induced interstitial lung disease in Japanese rheumatoid arthritis patients: A multi-drug hypersensitivity marker? (2013)
  • Author(s): Furukawa H, Oka S, Shimada K, Rheumatoid Arthritis associated Interstitial Lung Disease (RA-ILD) Study Consortium, Tsuchiya N, Tohma S.
  • Journal Title: Ann Rheum Dis. Volume: 72(1) Pages: 153-5
• [Journal Article] Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus (2013)
  • Author(s): Furukawa H, Kawasaki A, Oka S, Shimada K, Nakayama H, 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, Nagaoka S, Kono H, Okamoto A, Fukui N, Hashimoto H, Sumida T, Ono M, Tsuchiya N, Tohma S.
  • Journal Title: Lupus Volume: 22 Issue: 5 Pages: 497
  • DOI: 10.1177/0961203313479421
  • Peer Reviewed
• [Journal Article] Identification of a novel HLA allele, HLA-DQB1*06:51, in a Japanese rheumatoid arthritis patient. (2012)
  • Author(s): Oka S, Furukawa H, Kashiwase K, Tsuchiya N, Tohma S.
  • Journal Title: Tissue Antigens. Volume: 80(4) Pages: 386-7
• [Journal Article] Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: A protective role for shared epitope. (2012)
  • Author(s): Furukawa H, Oka S, Shimada K, Sugii S, Ohashi J, Matsui T, Ikenaka T, Nakayama H, Hashimoto A, Takaoka H, Arinuma Y, Okazaki Y, Futami H, Komiya A, Fukui N, Nakamura T, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S.
  • Journal Title: PLoS One. Volume: 7(5)
• [Journal Article] Association of PHRF1-IRF7 region polymorphism with clinical manifestations of systemic lupus erythematosus in a Japanese population. (2012)
  • Author(s): Kawasaki A, Furukawa H, Kondo Y, Ito S, Hayashi T, Kusaoi M, Matsumoto I, Tohma S, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N.
  • Journal Title: Lupus. Volume: 21(8) Pages: 890-5
  • NAID: 120007136865
• [Journal Article] Association of UBE2L3 polymorphisms with diffuse cutaneous systemic sclerosis in a Japanese population. (2012)
  • Author(s): Hasebe N, Kawasaki A, Ito I, Kawamoto M, Hasegawa M, Fujimoto M, Furukawa H, Tohma S, Sumida T, Takehara K, Sato S, Kawaguchi Y, Tsuchiya N.
  • Journal Title: Ann Rheum Dis. Volume: 71(7) Pages: 1259-60
• [Journal Article] TLR7 single nucleotide polymorphisms in the 3' untranslated region and intron independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study. (2011)
  • Author(s): Kawasaki A, Furukawa H, Kondo Y, Ito S, Hayashi T, Kusaoi M, Matsumoto I, Tohma S, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N.
  • Journal Title: Arthritis Res Ther. Volume: 13(2)
• [Journal Article] Association of TNFAIP3 interacting protein 1,TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study. (2010)
  • Author(s): Kawasaki A, Ito S, Furukawa H, Hayashi T, Goto D, Matsumoto I, Kusaoi M, Ohashi J, Graham RR, Matsuta K, Behrens TW, Tohma S, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N.
  • Journal Title: Arthritis Res Ther. Volume: 12(5)
• [Presentation] Genetic Background of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Japanese Population: Association of STAT4 with Myeloperoxidase Antineutrophil Cytoplasmic Antibody-Positive Vasculitis (2012)
  • Author(s): Kawasaki A, Inoue N, Ajimi C, Ito I, Sada K, Kobayashi S, Yamada H, Furukawa H, Tomita M, Sumida T, Tohma S, Miyasaka N, Ozaki S, Hashimoto H, Makino H, Harigai M and Tsuchiya N.
  • Organizer: Sixty-ninth Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: Washington D.C.
• [Presentation] Genetic background of ANCA-associated vasculitis in a Japanese population: a candidate gene study. (2012)
  • Author(s): Tsuchiya N, Kawasaki A, Ito I, Ajimi C, Kobayashi S, Yamada H, Furukawa H, Tohma S, Tomita M, Sumida T, Tokunaga K, Miyasaka N, Hashimoto H, Ozaki S, Makino H, Harigai M.
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012
  • Place of Presentation: Tokyo, Japan
• [Presentation] An association study of 8p23.1 region encoding BLK, FAM167A, C8orf12 and XKR6 with systemic lupus erythematosus in Japanese. (2010)
  • Author(s): Ito I, Ito S, Furukawa H, Hayashi T, Goto D, Matsumoto I, Takasaki Y, Hashimoto H, Tohma S, Sumida T, Tsuchiya N.
  • Organizer: Ninth International Congress on Systemic Lupus Erythematosus
  • Place of Presentation: Vancouver, British Columbia, Canada
• [Presentation] Association of TNFAIP3 and TNIP1 SNPs with systemic lupus erythematosus in a Japanese population. (2010)
  • Author(s): Kawasaki A, Ito S, Furukawa H, Hayashi T, Goto D, Matsumoto I, Graham RR, Behrens TW, Tohma S, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N.
  • Organizer: Ninth International Congress on Systemic Lupus Erythematosus
  • Place of Presentation: Vancouver, British Columbia, Canada