Analysis of the genetic background of Sjogren's syndrome

• Project/Area Number: 24591436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Hokkaido University
• Principal Investigator: Horita Tetsuya 北海道大学, 大学病院, 講師 (50399929)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シェーグレン症候群 / 疾患感受性遺伝子 / 遺伝子多型 / 一塩基多型 / 膠原病 / 自己免疫疾患

Outline of Final Research Achievements

Genomic DNA samples from 190 primary Sjogren's syndrome (SS) patients and ethnically matched 428 healthy controls were collected. Several lupus susceptible genes were evaluated using TaqMan Genotyping Assay. The allele frequencies of lupus risk in SS were significantly higher in BLK (odds ratio (OR) =1.61, 95% confidence interval (CI):1.21-2.15), STAT4 (OR=1.83, 95%CI:1.43-2.36), IRF5 (OR=1.40, 95%CI:1.07-1.82) and rs10798269 in 1q25.1 region (OR=1.62, 95%CI:1.20-2.18), compared with those in healthy controls. No significant associations were found in BANK1, TNFSF13, TNFAIP3 and TNFSF4. BLK, STAT4, IRF5 and 1q25.1 region were not only lupus susceptible genes but SS susceptible genes in Japanese population. SS share, in part, common genetic background with SLE.

Research Products

• [Journal Article] The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis. (2015)
  • Author(s): Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Amengual O, Horita T, Atsumi T.
  • Journal Title: Rheumatology (Oxford). Volume: 54 Pages: 1536-1536
  • DOI: 10.1093/rheumatology/kev192
  • Peer Reviewed
• [Journal Article] Takayasu arteritis and ulcerative colitis;high concurrence ratio and genetic overlap. (2015)
  • Author(s): Terao C, Matsumura T, Yoshifuji H, Kirino Y, Maejima Y, Nakaoka Y, Takahashi M, Amiya E, Tamura N, Nakajima T, Origuchi T, Horita T, Matsukura M, Kochi Y, Ogimoto A, Yamamoto M, Takahashi H, Nakayamada S, Saito K, Wada Y, Narita I, Kawaguchi Y, Yamanaka H, Ohmura K, Atsumi T, Tanemoto K, Miyata T, et al.
  • Journal Title: Arthritis Rheumatol. Volume: 印刷中 Pages: 2226-2232
  • DOI: 10.1002/art.39157
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comment on: The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis: reply. (2015)
  • Author(s): Yasuda S, Kurita T, Horita T, Atsumi T.
  • Journal Title: Rheumatology (Oxford) Volume: 54 Pages: 1129-1129
  • DOI: 10.1093/rheumatology/kev033
  • Peer Reviewed
• [Journal Article] β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome. (2015)
  • Author(s): Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H.
  • Journal Title: blood Volume: 125 Pages: 2835-2844
  • DOI: 10.1182/blood-2014-08-593624
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An independent validation of the Global Anti-Phospholipid Syndrome Score in a Japanese cohort of patients with autoimmune diseases (2015)
  • Author(s): Oku K, Amengual O, Bohgaki T, Horita T, Yasuda S, Atsumi T
  • Journal Title: Lupus. Volume: 24 Pages: 774-5
  • DOI: 10.1177/0961203314561284
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comment on: The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis: reply. (2015)
  • Author(s): Yasuda S, Kurita T, Horita T, Atsumi T.
  • Journal Title: Rheumatology (Oxford). Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] β2-glycoprotein I / HLA class II complexes are novel autoantigens in antiphospholipid syndrome. (2015)
  • Author(s): Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H.
  • Journal Title: Blood Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] An independent validation of the Global Anti-Phospholipid Syndrome Score in a Japanese cohort of patients with autoimmune diseases. (2015)
  • Author(s): Oku K, Amengual O, Bohgaki T, Horita T, Yasuda S, Atsumi T.
  • Journal Title: Lupus Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Coronary and mesenteric involvement in polyarteritis nodosa. (2015)
  • Author(s): Watanabe K, Yasuda S, Noguchi A, Horita T, Atsumi T.
  • Journal Title: Arthritis Rheumatol. Volume: 67 Pages: 583-583
  • DOI: 10.1002/art.38954
  • Peer Reviewed / Open Access
• [Journal Article] Ras guanine nucleotide-releasing protein 4 is aberrantly expressed in the fibroblast-like synoviocytes of patients with rheumatoid arthritis and controls their proliferation (2015)
  • Author(s): Kono M, Yasuda S, Stevens RL, Koide H, Kurita T, Shimizu Y, Kanetsuka Y, Oku K, Bohgaki T, Amengual O, Horita T, Shimizu T, Majima T, Koike T, Atsumi T.
  • Journal Title: Arthritis and Rheumatolgy Volume: 67 Pages: 396-407
  • DOI: 10.1002/art.38924
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The efficacy of tacrolimus in patients with interstitial lung diseases compacted with polymyositis or dermatomyositis (2015)
  • Author(s): Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Amengual O, Horita T, Atsumi T.
  • Journal Title: Rheumatology(Oxford) Volume: 54 Pages: 39-44
  • DOI: 10.1093/rheumatology/keu166
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Decreased expression of Runx1 and lowered proportion of Foxp3+ CD25+ CD4+ regulatory T cells in systemic sclerosis. (2015)
  • Author(s): Kataoka H, Yasuda S, Fukaya S, Oku K, Horita T, Atsumi T, Koike T
  • Journal Title: Modern Rheumatology Volume: 25 Pages: 90-95
  • DOI: 10.3109/14397595.2014.899736
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of antiphospholipid antibody measured by EliA anticardiolipin antibodies and anti-β2Glycoprotein I antibodies in antiphospholipid syndrome (2015)
  • Author(s): Fujieda Y, Shida H, Oku K, Bohgaki T, Amengual O, Horita T, Yasuda S, Atsumi T.
  • Journal Title: Japanese Journal of Clinical Immunology Volume: 37 Issue: 5 Pages: 430-436
  • DOI: 10.2177/jsci.37.430
  • NAID: 130004875940
  • Year and Date: 2015-01-06
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. (2014)
  • Author(s): Kono M, Yasuda S, Kato M, Kanetsuka Y, Kurita T, Fujieda Y, Otomo K, Horita T, Oba K, Kondo M, Mukai M, Yanai M, Fukasawa Y, Atsumi T
  • Journal Title: Autoimmun Rev. Volume: 23 Pages: 1124-1132
  • DOI: 10.1177/0961203314536246
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 5.Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility. (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H
  • Journal Title: Proc Natl Acad Sci U S A Volume: 111 Pages: 3787-3792
  • DOI: 10.1073/pnas.1401105111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies. (2014)
  • Author(s): Amengual O, Horita T, Binder W, Norman GL, Shums Z, Kato M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Yasuda S, Atsumi T
  • Journal Title: Rheumatology International Volume: 34 Pages: 1225-1230
  • DOI: 10.1007/s00296-014-2951-0
  • NAID: 120005656328
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The modifying effect of NAT2 genotype on the association between systemic lupus erythematosus and consumption of alcohol and caffeine-rich beverages. (2014)
  • Author(s): Kiyohara C1, Washio M, Horiuchi T, Asami T, Ide S, Atsumi T, Kobashi G, Takahashi H, Tada Y; Kyushu Sapporo SLE (KYSS) Study Group.
  • Journal Title: Arthritis Care Res Volume: 66 Pages: 1048-1056
  • DOI: 10.1002/acr.22282
  • Peer Reviewed / Open Access
• [Journal Article] Psychological stress in a Japanese population with systemic lupus erythematosus: finding from KYSS study. (2014)
  • Author(s): Takahashi H, Washio M, Kiyohara C, Tada Y, Asami T, Ide S, Atsumi T, Kobashi G, Yamamoto M, Horiuchi T; Kyushu Sapporo Sle (Kyss) Study Group.
  • Journal Title: Mod Rheumatol. Volume: 24 Pages: 448-452
  • DOI: 10.3109/14397595.2013.843745
  • Peer Reviewed / Open Access
• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility. (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 111 Pages: 3787-3792
  • Peer Reviewed
• [Journal Article] Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies. (2014)
  • Author(s): Amengual O, Horita T, Binder W, Norman GL, Shums Z, Kato M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Yasuda S, Atsumi T.
  • Journal Title: Rheumatol Int Volume: -
  • NAID: 120005656328
  • Peer Reviewed
• [Journal Article] The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis. (2014)
  • Author(s): Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Amengual O, Horita T, Atsumi T.
  • Journal Title: Rheumatology (Oxford). Volume: -
  • Peer Reviewed
• [Journal Article] Decreased expression of Runx1 and lowered proportion of Foxp3+ CD25+ CD4+ regulatory T cells in systemic sclerosis. (2014)
  • Author(s): Kataoka H, Yasuda S, Fukaya S, Oku K, Horita T, Atsumi T, Koike T.
  • Journal Title: Mod Rheumatol Volume: -
  • Peer Reviewed
• [Journal Article] Essential role of the p38 mitogen-activated protein kinase pathway in the tissue factor gene expression by the phosphatidylserine-dependent antiprothrombin antibody. (2013)
  • Author(s): Oku K, Amengual O, Zigon P, Horita T, Yasuda S, Atsumi T.
  • Journal Title: Rheumatol Volume: 52 Pages: 1775-1784
  • DOI: 10.1093/rheumatology/ket234
  • Peer Reviewed
• [Journal Article] The involvement of CD36 in the monocyte activation by antiphospholipid antibodies. (2013)
  • Author(s): Kato M, Atsumi T, Oku K, Amengual O, Nakagawa H, Fujieda Y, Otomo K, Horita T, Yasuda S, Koike T.
  • Journal Title: Lupus Volume: 22 Pages: 761-771
  • DOI: 10.1177/0961203313490242
  • NAID: 120005372328
  • Peer Reviewed
• [Journal Article] An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: effects of *09:01 allele on disease phenotypes (2013)
  • Author(s): Shimane K, Kochi Y, Suzuki A, Okada Y, Ishii T, Horita T, Saito K, Okamoto A, Nishimoto N, Myouzen K, Kubo M, Hirakata M, Sumida T, Takasaki Y, Yamada R, Nakamura Y, Kamatani N, Yamamoto K.
  • Journal Title: Rheumatology(Oxford) Volume: 52 Pages: 1172-1182
  • DOI: 10.1093/rheumatology/kes427
  • Peer Reviewed
• [Journal Article] Predominant prevalence of arterial thrombosis in Japanese patients with the antiphospholipid syndrome. (2013)
  • Author(s): Fujieda Y, Atsumi T, Amengual O, Odani T, Otomo K, Kato M, Oku K, Kon Y, Horita T, Yasuda S, Koike T
  • Journal Title: Lupus Volume: 21(14) Pages: 1506-14
  • DOI: 10.1177/0961203312458469
  • NAID: 120005356853
  • Peer Reviewed
• [Journal Article] Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome. (2013)
  • Author(s): Amengual O, Atsumi T, Oku K, Suzuki E, Horita T, Yasuda S, Koike T
  • Journal Title: Mod Rheumatol. Volume: 23(1) Pages: 81-8
  • DOI: 10.1007/s10165-012-0642-9
  • NAID: 10031167669
  • Peer Reviewed
• [Journal Article] Up-regulated expression of HLA-DRB5 transcripts and high frequency of the HLA-DRB5*01:05 allele in scleroderma patients with interstitial lung disease. (2012)
  • Author(s): Odani T, Yasuda S, Ota Y, Fujieda Y, Kon Y, Horita T, Kawaguchi Y, Atsumi T, Yamanaka H, Koike T.
  • Journal Title: Rheumatology (Oxford) Volume: 51 Pages: 1765-1774
  • Peer Reviewed
• [Journal Article] A Genome-Wide Association Study Identified (2012)
  • Author(s): 岡田随象
  • Journal Title: Plos Genetics Volume: (掲載確定) Pages: 1002455-1002455
  • DOI: 10.1371/journal.pgen.1002455
  • NAID: 120005906866
  • Peer Reviewed
• [Journal Article] Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. (2012)
  • Author(s): Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K, Horita T, Yasuda S, Koike T
  • Journal Title: Arthritis Rheum. Volume: 64 Pages: 504-12
  • DOI: 10.1002/art.33340
  • Peer Reviewed
• [Presentation] Haematopoietic stem cell transplantation for interstitial lung diseases in patients with systemic sclerosis; Therapeutic effect and evaluation of up-regulated genes. (2012)
  • Author(s): Yasuda S, Odani T, Ota Y, Fujieda Y, Kon Y, Horita T, Kawaguchi Y, Atsumi T, Yamanaka H, Koike T.
  • Organizer: The 8th international congress on autoimmunity
  • Place of Presentation: Palacio de Exposiciones y Congresos de Granada (Spain)
• [Presentation] The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis (2012)
  • Author(s): T. Kurita, S. Yasuda, K. Oba, K. Otomo, H. Shida, T. Watanabe, Y. Kanetsuka, M. Kono, T. Odani, Y. Fujieda, Y. Kon, T. Horita, N. Sato, T. Atsumi
  • Organizer: EULAR Annual European Congress of Rheumatology
  • Place of Presentation: Messe Berlin (Germany)
• [Presentation] Central nervous system involvements in systemic vasculitis. (2012)
  • Author(s): Kanetsuka T, Horita T, Watanabe T, Kono M, Kurita T, Fujieda Y, Odani T, Oku K, Bohgaki T, Yasuda S, Atsumi T.
  • Organizer: The 15th Congress of the Asia Pacific League of Associations for Rheumatology
  • Place of Presentation: the King Hussein Bin Talal Convention Center (Jordan)
• [Presentation] Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocyte (2012)
  • Author(s): Fujieda Y, Amengual O, Kanetsuka Y, Odani T, Otomo K, Oku K, Bohgaki T, Horita T, Yasuda S, Kuroki K, Maenaka K, Matsumoto M, Hatakeyama S, Atsumi T
  • Organizer: Annual Meeting of American College of Rheumatology
  • Place of Presentation: Walter E. Washington Convention Center (USA)
• [Presentation] Dual antiplatelet therapy as prophylaxis of recurrent arterial thrombosis in patients with antiphospholipid syndrome (2012)
  • Author(s): Fujieda Y, Amengual O, Watanabe T, Kono M, Kanetsuka Y, Kurita T, Odani T, Otomo K, Oku K, Bohgaki T, Horita T, Yasuda S, Atsumi T
  • Organizer: Annual Meeting of American College of Rheumatology
  • Place of Presentation: Walter E. Washington Convention Center (USA)