Stromelysin-1 polymorphism as a new potential risk factor in progression of chronic obstructive pulmonary disease

Monaldi Arch Chest Dis. 2009 Mar;71(1):15-20. doi: 10.4081/monaldi.2009.371.

Abstract

Background: Chronic obstructive lung disease (COPD) is characterised by partially reversible usually progressive airflow limitation caused by inflammation and remodelling. Stromelysin-1 (MMP-3) has regulatory activity on other matrix-metalloproteinases. Altered MMP-3 activity has been described in different diseases. We investigated the role of a promoter MMP-3 polymorphism in determining susceptibility and severity of COPD.

Methods: We studied 147 patients with COPD in stable conditions and distinguished two groups based on FEV1 values. In 100 patients functional modifications across a two-year period were noted. 133 healthy subjects were used as controls. Genotyping for the -1171 5A/6A MMP-3 polymorphism was performed using nucleotide sequencing.

Results: No difference was noted in the genotype distribution between COPD patients and controls. However, among patients with severe disease 6A/6A genotype and 6A allelic frequency were significantly more represented than among mild-moderate patients (p < 0.05). The 6A/6A genotype was also associated with a higher FEV1 decline over time.

Conclusions: Our data suggests that -1171 6A allele does not represent a risk factor for the development of COPD while it is associated with more severe disease and different functional decline. We hypothesis that a disregulation of MMP-3, possibly caused by the -1171 5A/6A polymorphism or other linked variants, may lead to different progression in COPD.

MeSH terms

  • Aged
  • Alleles
  • Analysis of Variance
  • Case-Control Studies
  • Chi-Square Distribution
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Matrix Metalloproteinase 3 / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Factors

Substances

  • Matrix Metalloproteinase 3