Stromelysin-1 polymorphism as a new potential risk factor in progression of chronic obstructive pulmonary disease.
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.
Santus
P
P
Institute of Lung Disease, University of Milan, Respiratory Unit, San Paolo Hospital, Milano, Italy.
Casanova
F
F
Biondi
M L
ML
Blasi
F
F
Di Marco
F
F
Centanni
S
S
D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors
D019278:Matrix Metalloproteinase 3