2018 Fiscal Year Final Research Report
Elucidation of pathophysiology and development of diagnosis method of non-alcoholic fatty liver disease by genomic and epigenomic analysis
| Project/Area Number |
16K09781
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Osaka University |
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Principal Investigator |
Hotta Kikuko 大阪大学, 医学部附属病院, 特任講師(常勤) (30360639)
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| Research Collaborator |
Nakajima Atsushi 横浜市立大学, 医学(系)研究科, 教授 (30326037)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 非アルコール性脂肪肝疾患 / RNAシークエンス / DNAメチル化 / 遺伝子共発現ネットワーク解析 / DMR |
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| Outline of Final Research Achievements |
RNA-sequencing and subsequent weighted gene co-expression network analysis of non-alcoholic fatty liver disease (NAFLD) revealed 2 networks associated with NAFLD, one of which is a scale-free network with 4 hub genes and the other is a random network. The genomic region that is under epigenetic regulation during NAFLD progression were identified using differentially methylated region (DMR) analyses. The average values of topological overlap measures for the CpG matrix combining two different DMRs were calculated and two DMR networks correlated with the stages of fibrosis were identified. The annotated genes of one network included genes involved in fibrosis and cellular proliferation. The annotated genes of the second network were associated with metabolic pathways. The CpG methylation levels in these networks were strongly affected by age and fasting plasma glucose levels. The methylation status of five DMRs in the second network was reversible following weight loss.
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| Free Research Field |
医歯薬学
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| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪肝疾患のゲノムワイドな発現解析、メチル化解析により病態進行に伴う変化が2-3個の遺伝子群に分類されることを明らかにすることが出来た。2-3個の遺伝子群の発現やメチル化レベルの変動には年齢、血糖値が重要であり、１つの遺伝子群は減量による可逆性が認められ、非アルコール性脂肪肝疾患における減量や血糖値コントロールの重要性が分子レベルで証明された。病態進行に関連する遺伝子群が少数のグループに分かれることから、メチル化レベルや発現量を調節する因子の存在が示唆された。それらの因子を同定することで新たな治療方法の開発が期待される結果となった。
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