Genetic exploration in the cause of developing rare lung diseases using whole exome sequence analyses

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09557
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tokyo Medical and Dental University (2018); Tokyo Medical University (2016-2017)
• Principal Investigator: SETOGUCHI Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 特任教授 (90206649)
• Research Collaborator: NAKAJIMA Toshihiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 特発性間質性肺炎 / PPFE / ゲノム / エクソーム解析 / 遺伝子 / サーファクタント / テロメア / 細胞接着因子

Outline of Final Research Achievements

Pleuroparenchymal fibroelastosis (PPFE) is a rare pulmonary fibrosis that is clinically characterized by upper lobe predominant fibrosis. The etiology remains unknown as well as other idiopathic interstitial pneumonias. To explore causative genes in developing PPFE as well as familial interstitial pneumonia (FIP), whole exome analyses or DNA sequence analyses with sanger method were performed in genome from 9 cases with adult-onset PPFE and 47 cases with adult-onset FIP. Deleterious variant in telomere-associated genes or cell adhesion factor associated genes were identified in all PPFE cases. Of FIP without PPFE, 57% was found to carry deleterious variants in surfactant-associated genes.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

稀少間質性肺炎PPFEを除く家族性間質性肺炎のほとんどは、サーファクタント関連遺伝子変異が、またPPFEにおいては、テロメア関連遺伝子変異或いはその遺伝子の転写後制御に関わるRNA変異が病態形成に関わっている可能性を明らかにした。これまで有効な治療もなく予後不良な間質性肺炎の一部であるが成因に関わる遺伝子を特定したことは、今後の治療方開発や予防への大きな糸口となることが期待される。