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