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

SETTING: Several matrix metalloproteinase (MMP) polymorphisms favouring the development of lung fi brosis 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 fi brosis 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 fi brosis by serial chest radiography for 1 year after completion of treatment. RESULTS: The frequency of the MMP-1(-1607G) polymorphism was signifi cantly higher in TB patients with moderate to advanced pulmonary fi brosis than in those with minimal to mild fi brosis. Having at least one-1607G MMP-1 polymorphism increased the risk of moderate and advanced fi brosis 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 fi brosis. The production of MMP-1 from monocytes stimulated by interleukin-1â 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 fi brosis 1 year after anti-tuberculosis treatment. This may be related to increased MMP-1 activity, leading to enhanced destruction of the matrix with subsequent fi brosis.