COPD Patient and Controls Group Three hundred thirty-five patients (248 males and 87 females) with COPD were enrolled in the study

COPD Patient and Controls Group Three hundred thirty-five patients (248 males and 87 females) with COPD were enrolled in the study. Abstract Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction. Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD. We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients. We analyzed SNP in the promoter region ofMMP-9gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals. Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) ofMMP-9(by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA). All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups. Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms. Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group. In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals. This phenomenon is probably associated with the disease-related lung environment but not with genetic features of theMMP-9MMP-9gene promoter was found to be associated with MMP-9 expression, and the -1562T allele leads to higher transcription activity [9]. In this study, we evaluated the role ofMMP-9gene -1562C/T polymorphism, as well as MMP-9 protein and its complexes with TIMP levels, in COPD development in Polish patients. 2. Materials and Methods 2.1. COPD Patient and Controls Group Three hundred thirty-five patients (248 males and 87 females) with COPD were enrolled in the study. All subjects underwent routine diagnosis including the spirometry result and FEV1/FVC ratio reduction below the lower limit of the norm. The spirometry test was performed twice, before the bronchodilator application (400?MMP-9gene (rs3918242) was typed by the PCR-RFLP method as described previously [9]. Briefly, Rocaglamide polymerase chain reactions were carried out in 20?p = 0.09gene (rs3918242) and copy number variability of gene in COPD patient and healthy control groups. Thymosin 1 Acetate gene polymorphismsMMP-9gene copies were analyzed in the groups of 60 randomly selected patients with COPD and 61 healthy volunteers. We found that 85.0% of COPD patients and 82.0% of controls had 2 copies of theMMP-9gene. Additionally, we also found individuals with 1 copy (3.3% and 4.9% in patients and controls, respectively), 3 copies (11.7% and 9.9% in patients and controls, respectively), and 4 copies (3.2% of controls). However, no significant difference in CNV frequency between COPD patients and the control group was found (Table 2). We also evaluated the levels of MMP-9 and its complexes with TIMP1 and TIMP2 in serum of COPD patients and controls (the same as selected for CNV) (Table 3). We found that the mean serum MMP-9 levels in the COPD group were significantly Rocaglamide higher in comparison with the control group (149.0?ng/ml versus 26.5?ng/ml; p 0.0001), as well as those of the controls subgroups with smoking status (27.5?ng/ml in smokers and 25.9?ng/ml in never smokers, p = 0.37 for comparison between both control subgroups). In contrast, there were no significant differences in the mean serum levels of MMP-9/TIMP1 and MMP-9/TIMP2 between the COPD patients and controls, except a significant difference between COPD patients and total controls in levels of MMP-9/TIMP1 complex (3146.8?pg/ml versus Rocaglamide 2970.1?pg/ml, p = 0.04). Additionally, serum of control smokers contained a significantly higher level of this complex in comparison to control nonsmokers (3135.8?pg versus 2869.8?pg, respectively; p = 0.03; Table Rocaglamide 3). Table 3 MMP-9, MMP-9/TIMP1, and MMP-9/TIMP2 proteins level in serum of COPD patient and healthy control groups. Proteins levelsMMP-9gene exhibited lower MMP-9 serum level in comparison to the combined group of patients with 1.