Kuo Han-Pin, Wang Yu-Min, Wang Chun-Hua, He Chih-Chen, Lin Shu-Min, Lin Horng-Chyuan, Liu Chien-Ying, Huang Kuo-Hsiung, Hsieh Ling-Ling, Huang Chien-Da
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 199 Tun-Hwa N. Rd., Taipei, Taiwan.
Tuberculosis (Edinb). 2008 May;88(3):262-7. doi: 10.1016/j.tube.2007.08.010. Epub 2007 Nov 8.
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.
支气管内膜结核（TB）常导致一定程度的气管支气管狭窄。由于基质金属蛋白酶（MMPs）在气道组织重塑中起重要作用，我们研究了MMP-1基因多态性在支气管内膜结核患者中的作用。对101例台湾肺结核患者进行MMP-1启动子（-1607 bp）的1G/2G基因分型。进行支气管镜检查以确定是否存在支气管内膜受累。还测定了外周血单核细胞和支气管活检组织中MMP-1的水平。MMP-1基因多态性的1G基因型，即至少含有一个1G等位基因，与支气管内膜结核的存在相关。通过多因素分析，1G基因型和女性性别是支气管内膜结核发生的独立预测因素。具有1G基因型的支气管内膜结核患者发生气管支气管狭窄的风险高9.86倍。IL-1β可增加1G基因型肺结核患者外周血单核细胞中MMP-1的水平。1G/1G基因型患者的支气管内膜结核肉芽肿中也存在MMP-1活性。MMP-1基因多态性的1G基因型通过上调MMP-1活性与发生气管支气管狭窄的较高风险相关。
