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Construction and validation of an algorithm for disease pathogenesis by exhaustive computational analysis

Research Project

Project/Area Number 18K19621
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Kinoshita Shigeru  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30116024)

Co-Investigator(Kenkyū-buntansha) 上田 真由美  京都府立医科大学, 医学(系)研究科(研究院), 特任准教授 (60398386)
岡田 随象  大阪大学, 医学系研究科, 教授 (70727411)
Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsStevens-Johnson症候群 / 感冒薬 / 遺伝子間相互作用 / IKZF1 / TLR3 / 遺伝子多型 / HLA / Whole genome sequence / De Novo mutation / 遺伝子多型間相互作用
Outline of Final Research Achievements

In this study, we were able to identify interactions between multiple disease-associated genes and their involvement in the pathogenesis of patients with common cold SJS, suggesting that multiple combinations of HLA types and gene polymorphisms may be able to predict patients more than 90% of the time. We also found that the disease-associated gene TLR3 not only interacted with HLA-A*02:06 and PTGER3 gene polymorphisms and markedly increased the risk of disease development, but also functionally interacted with other disease-associated genes IKZF1 and PTGER3. Thus, the multiple disease-associated genes and their gene-gene interactions found in the whole genome association analysis are also significantly involved in the pathogenesis of patients with cold sores SJS.

Academic Significance and Societal Importance of the Research Achievements

Stevens-Johnson症候群(SJS)とその重症型である中毒性表皮壊死症(TEN)は、医薬品の副作用で生じる薬疹の中で最も重篤で、いずれも突然発症して全身の皮膚と粘膜にびらんと水疱を生じ、SJSは約3%、TENは約20%の死亡率を有する。また、救命できても重篤な視力障害が後遺症となることが多い。原因薬剤は多岐にわたるが、市販の感冒薬並びに感冒時に病院で処方される非ステロイド抗炎症薬(NSAIDs)が原因薬剤として多く報告されている。本研究により感冒薬SJS発症の遺伝子素因、発症機序と病態が明らかになることにより、本疾患の予防ならびに早期診断・早期治療が可能となることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (11 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] ソウル大学/ヨンセイ大学/チョンナン大学(韓国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] LV眼研究所(インド)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] モアフィールド眼病院/バーミンガム大学(英国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] チュラロンコーン大学/マヒドン大学(タイ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] サンパウロ連邦大学(ブラジル)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2019 Research-status Report
  • [Journal Article] Human leukocyte antigen class I and II genes associated with dipyrone-related Stevens-Johnson syndrome and severe ocular complications in a Brazilian population2021

    • Author(s)
      Wakamatsu Tais Hitomi、Ueta Mayumi、Inoue Chikara、Costa Karita Antunes、Sakano Lais Yumi、Sallum Juliana Maria F.、Pereira Gomes Jose, lvaro、Kinoshita Shigeru
    • Journal Title

      The Ocular Surface

      Volume: 20 Pages: 173-175

    • DOI

      10.1016/j.jtos.2021.02.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mapping of susceptible variants for cold medicine-related Stevens-Johnson syndrome by whole-genome resequencing2021

    • Author(s)
      Kawai Yosuke、Hitomi Yuki、Ueta Mayumi、Khor Seik-Soon、Nakatani Ken、Sotozono Chie、Kinoshita Shigeru、Nagasaki Masao、Tokunaga Katsushi
    • Journal Title

      npj Genomic Medicine

      Volume: 6 Issue: 1 Pages: 9-17

    • DOI

      10.1038/s41525-021-00171-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human leukocyte antigen B*0702 is protective against ocular Stevens-Johnson syndrome/toxic epidermal necrolysis in the UK population2021

    • Author(s)
      Butt Gibran F.、Hassan Ali、Wallace Graham R.、Kinoshita Shigeru、Ahmad Sajjad、Ueta Mayumi、Rauz Saaeha
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 2928-2936

    • DOI

      10.1038/s41598-021-82400-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human leucocyte antigen association of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications in Han Chinese2021

    • Author(s)
      Ma Kevin Sheng-Kai、Chung Wen Hung、Hsueh Yi-Jen、Chen Shin-Yi、Tokunaga Katsushi、Kinoshita Shigeru、Ma David H K、Ueta Mayumi
    • Journal Title

      British Journal of Ophthalmology

      Volume: bjophthalmol~2020 Issue: 5 Pages: 317105-317105

    • DOI

      10.1136/bjophthalmol-2020-317105

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Topical application of toll-like receptor 3 inhibitors ameliorates chronic allergic skin inflammation in mice2021

    • Author(s)
      Tamagawa-Mineoka Risa、Ueta Mayumi、Arakawa Yukiyasu、Yasuike Risa、Nishigaki Hiromi、Okuno Yasushi、Hijikuro Ichiro、Kinoshita Shigeru、Katoh Norito
    • Journal Title

      Journal of Dermatological Science

      Volume: 101 Issue: 2 Pages: 141-144

    • DOI

      10.1016/j.jdermsci.2020.11.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of HLA polymorphisms and acetaminophen-related Steven-Johnson syndrome with severe ocular complications in Thai population2020

    • Author(s)
      Jongkhajornpong Passara、Ueta Mayumi、Lekhanont Kaevalin、Puangsricharern Vilavun、Prabhasawat Pinnita、Chantaren Patchima、Pisuchpen Phattrawan、Kinoshita Shigeru
    • Journal Title

      British Journal of Ophthalmology

      Volume: bjophthalmol~2020 Issue: 6 Pages: 317315-317315

    • DOI

      10.1136/bjophthalmol-2020-317315

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis.2020

    • Author(s)
      Yoshikawa Y, Ueta M, Nishigaki H, Kinoshita S, Ikeda T, Sotozono C.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 18922-18922

    • DOI

      10.1038/s41598-020-76064-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of gene expression by miRNA-455-3p,upregulated in the conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage.2020

    • Author(s)
      Ueta M, Nishigaki H, Sotozono C, Yokoi N, Mizushima K, Naito Y, Kinoshita S.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 17239-17239

    • DOI

      10.1038/s41598-020-74211-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HLA genotypes and cold medicine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications: a systematic review and meta-analysis2020

    • Author(s)
      Tangamornsuksan Wimonchat、Chanprasert Sirikan、Nadee Phenphechaya、Rungruang Saowalak、Meesilsat Natnaree、Ueta Mayumi、Lohitnavy Manupat
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 10589-10599

    • DOI

      10.1038/s41598-020-67610-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population2019

    • Author(s)
      Jun Ikhyun、Rim John Hoon、Kim Mee Kum、Yoon Kyung-Chul、Joo Choun-Ki、Kinoshita Shigeru、Seo Kyoung Yul、Ueta Mayumi
    • Journal Title

      British Journal of Ophthalmology

      Volume: 103 Issue: 4 Pages: 573-576

    • DOI

      10.1136/bjophthalmol-2018-313263

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association between HLA-B*44:03-HLA-C*07:01 haplotype and cold medicine-related Stevens-Johnson syndrome with severe ocular complications in Thailand2018

    • Author(s)
      Jongkhajornpong Passara、Lekhanont Kaevalin、Pisuchpen Phattrawan、Chantaren Patchima、Puangsricharern Vilavun、Prabhasawat Pinnita、Suphapeetiporn Kanya、Kinoshita Shigeru、Ueta Mayumi
    • Journal Title

      British Journal of Ophthalmology

      Volume: 102 Issue: 9 Pages: 1303-1307

    • DOI

      10.1136/bjophthalmol-2017-311823

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Cold medicine related Stevens-Johnson syndrome Associated with HLA-B*44:03 in various ethnic populations2018

    • Author(s)
      Mayumi Ueta, Passara Jongkhajornpong, Tais H. Wakamatsu, Chitra Kannabiran, Kaevalin Lekhanont, José Álvaro P. Gomes, Virender Sangwan, Chie Sotozono, Shigeru Kinoshita.
    • Organizer
      2018 American Academy of Ophthalmology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-07-25   Modified: 2022-01-27  

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