Investigation on pathogenesis of pulmonary diseases due to nontuberculous mycobacteria using human genomic analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03704
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Keio University
• Principal Investigator: HASEGAWA Naoki 慶應義塾大学, 医学部(信濃町), 教授 (20198724)
• Co-Investigator(Kenkyū-buntansha): 石井 誠 慶應義塾大学, 医学部(信濃町), 准教授 (30317333) ; 西村 知泰 慶應義塾大学, 保健管理センター(日吉), 講師 (90348649)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肺非結核性抗酸菌症 / 肺NTM症 / 肺MAC症 / モデルマウス / 気道上皮細胞

Outline of Final Research Achievements

Nontuberculous mycobacteria (NTM) causes chronic respiratory infection. Although NTM, including MAC bacteria, is a low-virulent mycobacteria in the environment, such as water and soil, pulmonary NTM disease occures mainly in middle-aged/older slender women, suggesting the existence of disease susceptibility genes. In this study, we conducted a genome-wide association study to compare genotypes between patients with pulmonary MAC disease and controls, and confirmed that genetic variation in the Calcineurin B homologous protein 2 (CHP2) region, which plays an important role in regulating intracellular and extracellular ions and pH, is highly associated with the risk of disease onset.

Free Research Field

感染症学、呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

世界で初めて肺 MAC 症患者と対照者との遺伝子型を網羅的に比較するゲノムワイド関連解析を実施し、細胞内外のイオンや pH の調整に重要な役割を担う Calcineurin B homologous protein2領域の遺伝的変異が発症リスクと高い関連性を示すことを確認しました。新たな治療戦略の開発および臨床現場においては疾患感受性遺伝子型に基づく個別化医療の実現に寄与する可能性が期待されます。