Matrix metalloproteinase-1 polymorphism in Taiwanese patients with endobronchial tuberculosis.
Endobronchial tuberculosis (TB) often leads to some degree of tracheobronchial stenosis. Because matrix metalloproteinases (MMPs) play an essential role in tissue remodeling in the airways, we investigated the role of MMP-1 polymorphism in patients with endobronchial TB. One hundred and one cases of pulmonary TB in Taiwanese patients were genotyped for the 1G/2G polymorphism of MMP-1 promoter (-1607 bp). Bronchoscopic examination was performed to determine the presence of endobronchial involvement. Levels of MMP-1 in peripheral blood monocytes and in bronchial biopsies were also determined. 1G genotypes of MMP-1 polymorphism, containing at least one 1G allele, were associated with the presence of endobronchial TB. Using multivariate analysis, 1G genotypes and female gender were independent predictors of the development of endobronchial TB. Endobronchial TB patients with 1G genotypes had a 9.86-fold greater risk of developing tracheobronchial stenosis. IL-1beta increased levels of MMP-1 in peripheral blood monocytes of TB patients with 1G genotypes. MMP-1 activity was also present in the endobronchial TB granuloma from patients with 1G/1G genotype. 1G genotypes of MMP-1 polymorphism were associated with a greater risk of developing tracheobronchial stenosis through up-regulation of MMP-1 activity.
Kuo
Han-Pin
HP
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tun-Hwa N. Rd., Taipei, Taiwan.
Wang
Yu-Min
YM
Wang
Chun-Hua
CH
He
Chih-Chen
CC
Lin
Shu-Min
SM
Lin
Horng-Chyuan
HC
Liu
Chien-Ying
CY
Huang
Kuo-Hsiung
KH
Hsieh
Ling-Ling
LL
Huang
Chien-Da
CD
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001980:Bronchi / Q000201:enzymology; D001982:Bronchial Diseases / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D014135:Tracheal Stenosis / Q000235:genetics / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D015854:Up-Regulation
D053583:Interleukin-1beta; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1