Elucidation of the genetic factors and the mechanisms of adverse effects by anti-rheumatic drugs.

• Project/Area Number: 26293123
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: University of Tsukuba (2015-2016); Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital (2014)
• Principal Investigator: FURUKAWA Hiroshi 筑波大学, 医学医療系, 准教授 (00372293)
• Co-Investigator(Kenkyū-buntansha): 當間 重人 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): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 遺伝子診断・治療 / 遺伝子診断治療

Outline of Final Research Achievements

It was tried to detect the genetic factors and the mechanisms of adverse effects by anti-rheumatic drugs. The genome wide association study was performed, but the results were not confirmed by the replication analysis. No specific micro RNA was detected in the plasma from the rheumatoid arthritis patients with methotrexate-induced interstitial lung diseases. The transgenic mouse of HLA-A*31:01, a susceptibility allele for methotrexate-induced interstitial lung diseases, was not more susceptible for the model of methotrexate-induced induced interstitial lung disease.

Research Products

• [Journal Article] Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. (2017)
  • Author(s): Terao C, Kawaguchi T, Dieude P, Varga J, Kuwana M, Hudson M, Kawaguchi Y, Matucci-Cerinic M, Ohmura K, Riemekasten G, Kawasaki A, Airo P, Horita T, Oka A, Hachulla E, Yoshifuji H, Caramaschi P, Hunzelmann N, Baron M, Atsumi T, Hassoun P, Torii T, Takahashi M, et al.
  • Journal Title: Ann Rheum Dis. Volume: 印刷中 Issue: 6 Pages: 1150-1158
  • DOI: 10.1136/annrheumdis-2016-210645
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial. (2017)
  • Author(s): Izumi Y, Akazawa M, Akeda Y, Tohma S, Hirano F, Ideguchi H, Matsumura R, Miyamura T, Mori S, Fukui T, Iwanaga N, Jiuchi Y, Kozuru H, Tsutani H, Saisyo K, Sugiyama T, Suenaga Y, Okada Y, Katayama M, Ichikawa K, Furukawa H, Kawakami K, Oishi K, Migita K.
  • Journal Title: Arthritis Res Ther. Volume: 19 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s13075-016-1207-7
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Common Protective Alleles HLA-DRB1*13 Among Systemic Autoimmune Diseases. (2017)
  • Author(s): Furukawa H, Oka S, Tsuchiya N, Shimada K, Hashimoto A, Tohma S, Kawasaki A.
  • Journal Title: Genes Immun. Volume: 18 Issue: 1 Pages: 1-7
  • DOI: 10.1038/gene.2016.40
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasma miRNA Expression Profiles in Rheumatoid Arthritis Associated Interstitial Lung Disease. (2017)
  • Author(s): Oka S, Furukawa H, Shimada K, Hashimoto A, Komiya A, Fukui N, Tsuchiya N, Tohma S.
  • Journal Title: BMC Musculoskelet Disord. Volume: 18 Issue: 1 Pages: 21-21
  • DOI: 10.1186/s12891-017-1389-4
  • NAID: 120007134825
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association of a single nucleotide polymorphism upstream of ICOS with Japanese autoimmune hepatitis type 1. (2017)
  • Author(s): Higuchi T, Oka S, Furukawa H, Nakamura M, Komori A, Abiru S, Nagaoka S, Hashimoto S, Naganuma A, Naeshiro N, Yoshizawa K, Shimada M, Nishimura H, Tomizawa M, Kikuchi M, Makita F, Yamashita H, Ario K, Yatsuhashi H, Tohma S, Kawasaki A, Ohira H, Tsuchiya N, Migita K.
  • Journal Title: J Hum Genet. Volume: in press Issue: 4 Pages: 481-484
  • DOI: 10.1038/jhg.2016.155
  • NAID: 40021158271
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Independent Association of HLA-G 3’ Untranslated Region 14bp Indel Polymorphism with Systemic Lupus Erythematosus in a Japanese Population: a Case-control Association Study. (2016)
  • Author(s): Hachiya Y, Kawasaki A, Oka S, Kondo Y, Ito S, Matsumoto I, Kusaoi M, Amano H, Suda A, Setoguchi K, Nagai T,Shimada K, Sugii S, Okamoto A, Chiba N, Suematsu E, Ohno S, Katayama M, Kono H, Hirohata S, Takasaki Y, Hashimoto H, Sumida T, Nagaoka S, Tohma S, Furukawa H, Tsuchiya N.
  • Journal Title: PLoS ONE. Volume: 11 Issue: 6 Pages: 22-22
  • DOI: 10.1371/journal.pone.0158065
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protective role of HLA-DRB1*13:02 against microscopic polyangiitis and MPO-ANCA positive vasculitis in a Japanese population: a case-control study. (2016)
  • Author(s): Kawasaki A, Hasebe N, Hidaka M, Hirano F, Sada K, Kobayashi S, Yamada H, Furukawa H, Yamagata K, Sumida T, Miyasaka N, Tohma S, Ozaki S, Matsuo S, Hashimoto H, Makino H, Arimura Y, Harigai M, Tsuchiya N.
  • Journal Title: PLoS ONE. Volume: 11 Issue: 5 Pages: e0154393-e0154393
  • DOI: 10.1371/journal.pone.0154393
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human Leukocyte Antigen and Systemic Sclerosis in Japanese: The Sign of the Four Independent Protective Alleles, DRB1*13:02, DRB1*14:06, DQB1*03:01, and DPB1*02:01. (2016)
  • Author(s): Furukawa H, Tohma S, Tsuchiya N, et al
  • Journal Title: PLoS One. Volume: 11(4) Issue: 4 Pages: e0154255-e0154255
  • DOI: 10.1371/journal.pone.0154255
  • NAID: 120007135446
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutrophil CD64 is upregulated in RA patients with lymphoma but not in other solid cancers. (2016)
  • Author(s): Komiya A, Matsui T, Horie K, Fukuda H, Iwata K, Tsuno H, Ogihara H, Ikenaka T, Kawakami M, Furukawa H, Hashimoto A, Hirai K, Tohma S.
  • Journal Title: Mod Rheumatol. Volume: 26 Issue: 2 Pages: 216-23
  • DOI: 10.3109/14397595.2015.1078986
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. (2015)
  • Author(s): Yasunami M, Nakamura H, Nakamura A, Yazaki M, Kishida D et al.
  • Journal Title: PLoS One Volume: May 14;10(5) Issue: 5 Pages: e0125938-e0125938
  • DOI: 10.1371/journal.pone.0125938
  • NAID: 120007100158
  • Peer Reviewed / Open Access
• [Journal Article] Autoantibody Profiles in Collagen Disease Patients with Interstitial Lung Disease (ILD): Antibodies to Major Histocompatibility Complex Class I-Related Chain A (MICA) as Markers of ILD. (2015)
  • Author(s): Furukawa H, Oka S, Shimada K, Masuo K, Nakajima F, Funano S, Tanaka Y, Komiya A, Fukui N, Sawasaki T, Tadokoro K, Nose M, Tsuchiya N, Tohma S.
  • Journal Title: Biomark Insights. Volume: 16 Pages: 63-73
  • DOI: 10.4137/bmi.s28209
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy. (2015)
  • Author(s): Migita K, Iwanaga N, Imadachi S, Jiuchi Y, Izumi Y, Tsuji Y, Kawahara C, Kawakami A, Furukawa H, Tohma S.
  • Journal Title: Medicine (Baltimore) Volume: 94 Issue: 27 Pages: e875-e875
  • DOI: 10.1097/md.0000000000000875
  • NAID: 120006986908
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Circulating microRNA Profiles in Patients with Type-1 Autoimmune Hepatitis. (2015)
  • Author(s): Migita K, Komori A, Kozuru H, Jiuchi Y, Nakamura M, Yasunami M, Furukawa H, Abiru S, Yamasaki K, Nagaoka S, Hashimoto S, Bekki S, Kamitsukasa H, Nakamura Y, Ohta H, Shimada M, Takahashi H, et al.
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: e0136908-e0136908
  • DOI: 10.1371/journal.pone.0136908
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Incidence of malignancy and the risk of lymphoma in Japanese rheumatoid arthritis patients compared to the general population. (2015)
  • Author(s): Hashimoto A, Chiba N, Tsuno H, Komiya A, Furukawa H, Matsui T, Nishino J, Tohma S.
  • Journal Title: J Rheumatol. Volume: 42 Issue: 4 Pages: 564-71
  • DOI: 10.3899/jrheum.140533
  • Peer Reviewed
• [Journal Article] Predictors of mortality in patients with interstitial lung disease treated with corticosteroids: results from a cohort study. (2014)
  • Author(s): Migita K, Arai T, Jiuchi Y, Izumi Y, Iwanaga N, Kawahara C, Suematsu E, Miyamura T, Tsutani H, Kawabe Y, Matsumura R, Mori S, Ohshima S, Yoshizawa S, Suenaga Y, Ogushi F, Kawabata M, Furukawa H, Matsui T, Bito S, Tohma S.
  • Journal Title: Medicine (Baltimore). Volume: 93 Issue: 26 Pages: e175-e175
  • DOI: 10.1097/md.0000000000000175
  • Peer Reviewed
• [Journal Article] Protective effect of the HLA-DRB1*13:02 allele in Japanese rheumatoid arthritis patients. (2014)
  • Author(s): Oka S, Furukawa H, Kawasaki A, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Ito S, Nakamura T, Saisho K, Katayama M, Tsunoda S, Sano H, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S.
  • Journal Title: PLoS One. Volume: 9 Issue: 6 Pages: e99453-e99453
  • DOI: 10.1371/journal.pone.0099453
  • Peer Reviewed / Open Access
• [Journal Article] HLA-DRB1*08:02 is associated with bucillamine-induced proteinuria in Japanese rheumatoid arthritis patients. (2014)
  • Author(s): Furukawa H, Oka S, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Miyashita T, Migita K, Suda A, Nagaoka S, Tsuchiya N, Tohma S.
  • Journal Title: Biomark Insights. Volume: 9 Pages: 23-8
  • DOI: 10.4137/bmi.s13654
  • Peer Reviewed / Open Access
• [Presentation] HLAクラスIIと強皮症 (2017)
  • Author(s): 古川宏,岡笑美,川崎綾,島田浩太,杉井章二,松下貴史,橋本篤,小宮明子,福井尚志,小林幸司,長田侑,井畑淳,近藤裕也,永井立夫,瀬戸口京吾,岡本明子,岡本享,千葉実行,末松栄一,河野肇,片山雅夫,廣畑俊成,住田孝之,右田清志,長谷川稔,藤本学,佐藤伸一,長岡章平,竹原和彦,當間重人,土屋尚之
  • Organizer: 第20回強皮症研究会議
  • Place of Presentation: アステラス製薬 本社(東京都中央区)
  • Year and Date: 2017-01-14
• [Presentation] 関節リウマチ関連間質性肺病変における血漿中miRNA (2016)
  • Author(s): 岡笑美,古川宏,島田浩太,橋本篤,小宮明子,土屋尚之,當間重人
  • Organizer: 第70回国立病院総合医学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県宜野湾市)
  • Year and Date: 2016-11-11
• [Presentation] 日本人全身性エリテマトーデスとHLA-G多型の関連 (2016)
  • Author(s): 川崎綾,八谷有紀,古川宏,近藤裕也,伊藤聡,松本功,草生真規雄,天野浩文,須田昭子,長岡章平,瀬戸口京吾,永井立夫,廣畑俊成,島田浩太,杉井章二,岡本享,千葉実行,末松栄一,大野滋,片山雅夫,河野肇,髙崎芳成,橋本博史,住田孝之,當間重人,土屋尚之
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-04-21
• [Presentation] 関節リウマチに合併する間質性肺病変と血漿中miRNA発現 (2016)
  • Author(s): 岡笑美,古川宏,島田浩太,橋本篤,小宮明子,土屋尚之,當間重人
  • Organizer: 第60回日本リウマチ学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-04-21
• [Presentation] Association of HLA-G and Leukocyte Immunoglobulin-like Receptor A3 Polymorphisms with the Susceptibility to Pulmonary Hypertention in Systemic Sclerosis. (2015)
  • Author(s): Hachiya Y, Kawasaki A, Matsushita T, Furukawa H, Nagaoka S, Shimada K, Sugii S, Setoguchi K, Okamoto A, Chiba N, Suematsu E, Katayama M, Hirohata S, Kono H, Migita K, Sumida T, Tohma S, Hasegawa M, Fujimoto M, Sato S, Takehara K, Tsuchiya N.
  • Organizer: Seventy-second Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: San Francisco
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] Anti-Major Histocompatibility Complex Class I-Related Chain A (MICA) Antibodies in Rheumatoid Arthritis Patients with Interstitial Lung Disease. (2014)
  • Author(s): Furukawa H, Oka S, Shimada K, Komiya A, Fukui N, Tsuchiya N, Tohma S
  • Organizer: Seventy-first Annual Scientific Meeting of American College of Rheumatology
  • Place of Presentation: Boston
  • Year and Date: 2014-11-14 – 2014-11-19
• [Book] 「強皮症の基礎と臨床：病態の解明から最新の診療まで」（佐藤伸一編） (2016)
  • Author(s): 八谷有紀,古川宏,土屋尚之:遺伝因子 共著 分担執筆
  • Total Pages: 10
  • Publisher: 医薬ジャーナル社