| Project/Area Number |
12470138
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
YAMAGUCHI Kazuhiro School of Medicine, Department of Medicine Associate Professor, 医学部, 助教授 (30129712)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Yoko School of Medicine, Department of Medicine Assistant, 医学部, 助手 (90286451)
OYAMADA Yoshitaka School of Medicine, Department of Medicine Assistant, 医学部, 助手 (00233627)
NAKAMURA Hidetoshi School of Medicine, Department of Medicine Assistant, 医学部, 助手 (00217879)
MINEMATSU Naoto School of Medicine, Department of Medicine Assistant, 医学部, 助手 (20296578)
TATENO Hiroki School of Medicine, Department of Medicine Assistant, 医学部, 助手 (50286473)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | pulmonary emphysema / smoking / chest CT / MMP-9 / cathepsin S / cystatin C / CYP2A6 / cystatin C / MMP-1 / TIMP-2 / 肺機能 / Cathepsin S / HRCT / 経年変化 |
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| Research Abstract |
COPD is defined by airflow obstruction caused by various mechanisms including alveolar destruction, airway hypersecretion, fibrosis of the airway wall, and remodeling of pulmonary vasculature. Genetic polymorphisms may be responsible for each process of the development of COPD. The present study aimed to elucidate the genetic factors involved in emphysematous changes of the lung in Japanese smokers by introducing diffusing capacity, low attenuation area score and the diameter of main pulmonary artery on chest CT images, and quantitative measures of exposure to smoking, as analytical parameters of COPD phenotypes, in addition to FEV1.0 which was solely utilized for genetical studies of COPD. Our study demonstrated that genetic polymorphisms in MMP-9 and cathepsin S, both of which are known to have potent elastase activity derived from alveolar macrophages, contribute to sensitivity to smoking for the development of pulmonary emphysema. In addition, CYP_2A_6, which metabolizes nicotine and activates procarcinogens, was related to emphysematous changes besides its effect on smoking habit. Genetic polymorphism of cystatin C, a main inhibitor of cathepsin S, was associated with the diameter of pulmonary artery, suggesting its role in the remodeling of pulmonary artery. CYP_2A_6 deletion polymorphism was also related to the tendency to become habitual smokers and the difficulty in cessation of smoking. These results suggest that smoking cessation programs including genetical analysis will give smokers a stronger motivation to quit smoking and help them utilize nicotine replacement therapy. Moreover, if genetical factors for individual phenotypes of COPD were identified, the pathogenesis of this complex category of pulmonary diseases may be better understood and the appropriate treatment for each disease process may be developed.
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