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Free Content MMP-1(-1607G) polymorphism as a risk factor for fibrosis after pulmonary tuberculosis in Taiwan

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Abstract:

SETTING: Several matrix metalloproteinase (MMP) polymorphisms favouring the development of lung fibrosis after pulmonary tuberculosis (TB) have been described.

OBJECTIVE: To investigate the association of MMP-1, MMP-9 and MMP-12 polymorphisms with the development of fibrosis in pulmonary TB.

DESIGN: We studied 49 normal subjects and 98 TB patients. We analysed the association between MMP polymorphisms and clinical indices of lung fibrosis by serial chest radiography for 1 year after completion of treatment.

RESULTS: The frequency of the MMP-1(-1607G) polymorphism was significantly higher in TB patients with moderate to advanced pulmonary fibrosis than in those with minimal to mild fibrosis. Having at least one -1607G MMP-1 polymorphism increased the risk of moderate and advanced fibrosis respectively by 5.04 (95%CI 1.25–20.30) and 9.87 (95%CI 2.39–40.88) fold. There was no association of MMP-9(-1562T) and MMP-12(Asn357Ser) polymorphisms with lung fibrosis. The production of MMP-1 from monocytes stimulated by interleukin-1β was increased in subjects with the 1G allele genotype compared to the 2G/2G genotype.

CONCLUSIONS: Patients with MMP-1(-1607G) polymorphism are more vulnerable to more extensive lung fibrosis 1 year after anti-tuberculosis treatment. This may be related to increased MMP-1 activity, leading to enhanced destruction of the matrix with subsequent fibrosis.

Keywords: genetic polymorphisms; lung fibrosis; matrix metalloproteinase-1; matrix metalloproteinase-12; tuberculosis

Document Type: Regular Paper

Affiliations: 1: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; and Department of Chinese Medicine, Chang Gung University, Taoyuan, Taiwan 2: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan 3: Department of Public Health, Chang Gung University, Taoyuan, Taiwan 4: National Heart and Lung Institute, Imperial College, London, UK 5: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; and Department of Medicine, Chang Gung University, Taoyuan, Taiwan

Publication date: May 1, 2010

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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