MMP-1(-1607G) Polymorphism As a Risk Factor for Fibrosis After Pulmonary Tuberculosis in Taiwan

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-1 beta 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.