The selected genetic polymorphisms of metalloproteinases MMP2, 7, 9 and MMP inhibitor TIMP2 in sarcoidosis
Wojciech J. Piotrowski, Pawel Gorski, Tadeusz Pietras, Wojciech Fendler, Janusz Szemraj
Med Sci Monit 2011; 17(10): CR598-607
Available online: 2011-10-01
Background: Increased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis, and may also be one of the factors responsible for the development of lung fibrosis. The aim of this study was to verify whether polymorphisms of MMP2 C-735T, MMP7 A-181G, MMP9 T-1702A and tissue inhibitor of metalloproteinase (TIMP)2 G-418C predispose to sarcoidosis.
Material/Methods: The study included 139 patients with sarcoidosis and 100 healthy subjects. MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR. DNA for genetic polymorphism was extracted from peripheral blood by GTC method. Protein concentrations in peripheral blood lysates were measured by ELISA, and MMP2 and 9 activities in BAL fluid were estimated by gel zymography.
Results: TT genotype in MMP9 T-1702A was more frequent in sarcoidosis (p<0.0001, OR=13.71, 95% CI 7.02–26.80) and resulted in higher expression of MMP9 mRNA (p<0.0001). No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome. There were no differences in the distribution of MMP2, MMP7 and TIMP2 polymorphisms. Messenger RNAs, as well as protein concentrations of MMP2, 7, 9, and TIMP2 were elevated in patients with sarcoidosis (p<0.0001 for each).
Conclusions: The TT homozygotes of MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and TIMP2 mRNAs suggest their inducibility.
Keywords: Sarcoidosis - genetics, Reverse Transcriptase Polymerase Chain Reaction, Real-Time Polymerase Chain Reaction, Polymorphism, Single Nucleotide - genetics, Poland, Matrix Metalloproteinase 9 - genetics, Matrix Metalloproteinase 7 - genetics, Matrix Metalloproteinase 2 - genetics, Genetic Predisposition to Disease - genetics, Enzyme-Linked Immunosorbent Assay, DNA Primers - genetics, Bronchoalveolar Lavage Fluid - chemistry, Tissue Inhibitor of Metalloproteinase-2 - genetics