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.
|Number of pages||6|
|Journal||Monaldi Archives for Chest Disease - Cardiac Series|
|Publication status||Published - Mar 2009|
- Candidate genes
- Genetic polymorphisms
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine