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

P. Santus, F. Casanova, M. L. Biondi, F. Blasi, F. Di Marco, Stefano Centanni

Research output: Contribution to journalArticlepeer-review

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 FEV 1 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 MNIP-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 FEV 1 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 hypothesise 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.

Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalMonaldi Archives for Chest Disease - Cardiac Series
Volume71
Issue number1
Publication statusPublished - Mar 2009

Keywords

  • Candidate genes
  • COPD
  • Genetic polymorphisms
  • Genotype
  • Matrix-metalloproteinases
  • Stromelysin-1

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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