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


METHODS
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.
Wang
C-H
CH
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Lin
H-C
HC
Lin
S-M
SM
Huang
C-D
CD
Liu
C-Y
CY
Huang
K-H
KH
Hsieh
L-L
LL
Chung
K F
KF
Kuo
H-P
HP
D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D053508:Matrix Metalloproteinase 12 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy
D000995:Antitubercular Agents; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1