Construction and validation of an algorithm for disease pathogenesis by exhaustive computational analysis
| Project/Area Number |
18K19621
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Kinoshita Shigeru 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30116024)
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| 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)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| Keywords | Stevens-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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(18 results)
