Abstract
Background
Major
symptoms of chronic obstructive pulmonary disease (COPD) are chronic
bronchitis and emphysema leading from lung tissue destruction, that is
an effect of an imbalance between metalloproteinases (MMPs) and their
tissue inhibitors activity. As potential factor involved in this COPD
pathogenesis, MMP-12 is considered. We investigated the role of genetic
polymorphism and protein level of MMP-12 in the COPD development among
Poles.
Methods
We
analyzed ??82 A?>?G SNP in the promoter region of MMP-12 gene
(rs2276109) among 335 smoked COPD patients and 309 healthy individuals,
including 110 smokers. Additionally, 60 COPD patients and 61 controls
(23 smokers) were tested for serum levels of MMP-12 using ELISA. All
subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters).
Results
We
observed that -82G allele and -82GG homozygous genotype frequencies of
the SNP rs2276109 were significantly lower in COPD patients than in
controls (12.5% vs 16.9%, respectively; X2?=?4.742, p?=?0.02 for allele and 0.5% vs 3.9%, respectively; X2?=?9.0331,
p?=?0.01 for genotype). Moreover, -82G allele was more frequent in
controls smokers than in non-smokers (22.3% vs 14.1%, X2?=?6.7588,
p?=?0.01). Serum level of MMP-12 was significantly higher in COPD
patients than in controls groups (6.8?ng/ml vs 3.3?ng/ml, respectively;
F?=?7.433, p?<?0.0001), although independently of analyzed gene
polymorphisms. Additionally, no correlation between parameters of lung
function (FEV1% and FEV1/FVC) and protein level was found.
Conclusions
We
found that -82G allele of SNP rs2276109 was associated with reduced
risk of COPD, and COPD patients released more MMP-12 than healthy
individuals, but independently on this SNP.
Keywords
COPD Metalloproteinase 12 Genetics SNP ELISA
