Elucidation of host susceptibility to pulmonary NTM disease and bronchiectasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15667
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Keio University
• Principal Investigator: Namkoong Ho 慶應義塾大学, 医学部(信濃町), 講師 (50594644)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: NTM / MAC / 疾患感受性遺伝子 / CHP2 / CFTR

Outline of Final Research Achievements

We performed the world's first GWAS for pulmonary MAC disease and identified a disease susceptibility SNP (rs109592) in the CHP2 gene region. Retention of risk alleles for pulmonary MAC disease significantly reduced CHP2 expression in the lungs, and CHP2 regulates pH via NHE expressed in epithelial cells, suggesting that airway epithelial cells may play an important role in pulmonary MAC disease. Facilitated an international host genome study of pulmonary NTM disease using 722 Korean (1722 controls) and 276 American (276 controls) patients with pulmonary MAC disease to show that rs109592, located in the CHP2 region, is a risk for pulmonary MAC disease across populations.

Free Research Field

呼吸器感染症

Academic Significance and Societal Importance of the Research Achievements

肺MAC症に対するGWASを世界に先駆けて報告し、疾患感受性遺伝子CHP2の機能解析は発展性が高い。既に申請者を中心に大規模なコホート研究(UMIN000007546)を有しており、臨床情報や検体を確実に収集できる体制にあるため、本研究結果を検証可能な状況にあり、基礎的研究成果の意義の臨床的検証が展開できる。研究代表者の肺MAC症のGWASの発表以降、世界中の多くの研究者が肺NTM症の宿主因子に取り組む中で、研究代表者は米国・欧州・豪州・韓国・台湾の研究者と共にNTM Host Research Consortiumの国際共同研究ネットワークを拡大し、国際共同研究を推進できるようになった。