title: Matrix metalloproteinase-1 polymorphism (-1607G) and disease severity in non-cystic fibrosis bronchiectasis in Taiwan.
abstract: OBJECTIVE
  Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis.
  
  
  METHODS
  To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed.
  
  
  RESULTS
  The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p<0.01). Forced expiratory volume in 1 second (FEV1) was decreased in bronchiectasis patients with 1G/1G (1.2±0.1 L, n = 14) and 1G/2G (1.3±0.1 L, n = 66) genotypes compared to the 2G/2G genotype (1.7±0.1 L, n = 33, p<0.01). Six minute walking distance was decreased in bronchiectasis patients with 1G/1G and 1G/2G compared to that of 2G/2G genotype. Disease severity evaluated by HRCT score significantly increased in bronchiectasis patients with 1G/1G and 1G/2G genotypes compared to that of 2G/2G genotype. Bronchiectasis patients with at least one MMP-1 (-1607G) allele showed increased tendency for hospitalization. Serum levels of pro-MMP-1, active MMP-1 and TGF-β1 were significantly increased in patients with bronchiectasis with 1G/1G and 1G/2G genotype compared with 2G/2G genotype or normal subjects. Under IL-1β stimulation, peripheral blood monocytes from subjects with 1G/2G or 1G/1G genotype secreted higher levels of TGF-β1compared to subjects with 2G/2G genotype.
  
  
  CONCLUSIONS
  This is the first report to address the influence of MMP-1 polymorphisms on lung function and airway destruction in non-CF bronchiectasis patients. Bronchiectasis patients with MMP-1(-1607G) polymorphism may be more vulnerable to permanent lung fibrosis or airway destruction due to the enhanced MMP-1 and TGF-β1 activity. Upregulated MMP-1 activity results in proteolytic destruction of matrix, and leads to subsequent fibrosis.
authors.affiliation: Department of Thoracic Medicine, Chang Gung Medical Foundation, Taipei, Taiwan.
authors.forename: Meng-Heng
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Pai-Chien
authors.initials: PC
authors.lastname: Chou
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chou
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Ho
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Joa
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Chen
authors.forename: Te-Fang
authors.initials: TF
authors.lastname: Sheng
authors.forename: Horng-Chyuan
authors.initials: HC
authors.lastname: Lin
authors.forename: Tsai-Yu
authors.initials: TY
authors.lastname: Wang
authors.forename: Po-Jui
authors.initials: PJ
authors.lastname: Chang
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000483:Alleles; D001987:Bronchiectasis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013624:Taiwan
chemical_list: D020781:Matrix Metalloproteinase 1