Endotypes of Refractory Airway Diseases: A Comprehensive Genomic Exploration of Gene Networks

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03663
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: University of Tsukuba
• Principal Investigator: Hizawa Nobuyuki 筑波大学, 医学医療系, 教授 (00301896)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 喘息 / COPD / エンドタイプ / ネットワーク / CDHR3 / ORMDL3

Outline of Final Research Achievements

Behind the diverse phenotypes of asthma and COPD, there are complex molecular networks (endotypes) driven by multiple genetic and environmental factors, and the elucidation of molecular networks established by gene-gene interactions is essential for understanding their pathogenesis. In this study, we specifically identified 1) the interaction between rhinovirus susceptibility CDHR3 gene and atopy-related genetic risk score in the development of asthma and COPD, 2) the interaction between CDHR3 gene and ORMDL3 gene, an ER stress response molecule, and 3) the significant associations between eQTLs at the ETS translocation variant (ETV4), which defines asthma-related gene expression network, and asthma development as well as serum IL-6 levels in healthy subjects.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

CDHR3遺伝子の喘息発症に及ぼす影響は、Atopy-GRSやORMDL3遺伝子の影響を強く受けていることが判明した。また、IL-6やTh17と関連する転写因子ETV4が幅広く喘息と関連することが明らかとなった。本研究の成果は、好中球性炎症やライノウイルス感受性分子ネットワークに関連したバイオマーカーや新規治療ターゲットの同定、さらには病名ではなく患者ごとにエンドタイプに基づいたPrecision Medicine（精密医療）やPreemptive Medicine（先制医療）を可能とするための基盤データの創出につながる。