PT - JOURNAL ARTICLE AU - Wojciech J. Piotrowski AU - Pawel Gόrski AU - Tadeusz Pietras AU - Janusz Szemraj TI - The genetic polymorphism of metalloproteinases MMP2, 7, 9 and MMP inhibitor TIMP2 in sarcoidosis DP - 2011 Sep 01 TA - European Respiratory Journal PG - p2000 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p2000.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p2000.full SO - Eur Respir J2011 Sep 01; 38 AB - Background: Increased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis. It may also be one of the factors responsible for the development of lung fibrosis. The aim was to verify whether polymorphisms of MMP2 C735T, MMP7 A181G, MMP9 T1702A and tissue inhibitor of metalloproteinase (TIMP)2 G418C predispose to sarcoidosis.Material and methods: 139 patients with sarcoidosis and 100 healthy subjects were included. 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 T1702A 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). There was no relation to radiological stages, 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. MMP2, 7, 9 and TIMP2 mRNAs, as well as concentrations of these molecules were elevated (p<0.0001 for each). Gel zymography did not show differences in MMP2 and MMP9 activity in BAL fluid between different genotypes.Conclusions: The TT homozygotes of MMP9 T1702A genotype may be predisposed to sarcoidosis. Elevated mRNAs of all these molecules suggest their inducibility.This study was supported by the Medical University of Lodz (grant No 502 -16-807) and Polish Ministry of Science (grant NN 402 350838).