Division of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland.
Med Sci Monit. 2011 Oct;17(10):CR598-607. doi: 10.12659/msm.881987.
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.
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).
The TT homozygotes of MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and TIMP2 mRNAs suggest their inducibility.
金属蛋白酶活性的增加可能在结节病的炎症发生和发展中起作用，也可能是导致肺纤维化发展的因素之一。本研究旨在验证 MMP2 C-735T、MMP7 A-181G、MMP9 T-1702A 和组织金属蛋白酶抑制剂（TIMP）2 G-418C 基因多态性是否易患结节病。
材料/方法：研究纳入 139 例结节病患者和 100 例健康对照者。采用实时 RT-PCR 检测外周血裂解物中 MMPs 和 TIMP2mRNA 的表达。采用 GTC 法从外周血中提取 DNA 进行遗传多态性检测。采用 ELISA 法检测外周血裂解物中蛋白浓度，采用凝胶酶谱法估计 BAL 液中 MMP2 和 9 的活性。
MMP9 T-1702A 的 TT 基因型在结节病中更为常见（p<0.0001，OR=13.71，95%CI7.02-26.80），并导致 MMP9mRNA 的表达增加（p<0.0001）。TT 和 AT/AA 患者在影像学分期、肺功能试验参数、活动标志物以及 Löfgren 综合征的存在/缺失方面无差异。MMP2、MMP7 和 TIMP2 多态性的分布无差异。MMP2、7、9 和 TIMP2 的信使 RNA 以及蛋白浓度在结节病患者中均升高（p<0.0001）。
MMP9 T-1702A 基因型的 TT 纯合子可能易患结节病。升高的 MMP2、7、9 和 TIMP2mRNA 表明它们的诱导性。
