2019 Fiscal Year Final Research Report
Development of the diagnostic methods to predict the development and the prognosis of autoimmune diseases based on the genome and epigenome informations
| Project/Area Number |
17H04111
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
日高 洋 大阪大学, 医学系研究科, 准教授 (30243231)
渡邉 幹夫 大阪大学, 医学系研究科, 教授 (50294088)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 自己免疫疾患 / 甲状腺 / 病因・病態 / 発症予測 / 遺伝子多型 / エピジェネティクス / マイクロRNA / DNAメチル化 |
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| Outline of Final Research Achievements |
In order to develop the predictive diagnostic method for the development and prognosis of autoimmune disease, we examined genetic and epigenetic factors in autoimmune thyroid disease (AITD). Then, we found that gene polymorphisms of thyroid-specific antigens (Tg and TPO) and costimulatory molecules which induce regulatory T cells (CD58) and helper T (Th) cells (CD80/CD86) were the genetic factors for the development of AITD, and that micro RNA (miR-146a), which suppresses NF-κB activity via TRAF6, and DNA methylation of TNFA gene polymorphisms were the environmental factors for the disease development. On the other hand, we found that gene polymorphisms of various factors which regulate Th1 and Th17 cells (IL18, MIR27A, CRTH2, IL17F, IL15, TLR7/TLR9, AGO2 and et al.) were the genetic factors for the prognosis (severity) of AITD, and that DNA methylations of IFNG and IL6 genes were the epigenetic factors for the disease prognosis.
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| Free Research Field |
自己免疫性甲状腺疾患の病因・病態
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| Academic Significance and Societal Importance of the Research Achievements |
単純に疾患と健常人を比較する今までのゲノムワイド関連解析等で解明された自己免疫疾患の遺伝因子はオッズ比が低く、疾患の発症予測等には利用できない。そこで、疾患の病態分類を厳密かつ詳細に行って解析した結果、オッズ比の高い結果が得られた。さらに、疾患の発症には、遺伝因子以外に環境因子も関与しているため、環境因子の影響を受けて遺伝子の発現を変化させるエピジェネティック因子（micro RNA、DNAメチル化など）を解明することにした。そして、これらのエピジェネティック因子の解明により、有用な自己免疫疾患の発症・予後予測診断法の開発が可能になった。
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