The Association of MCP-1 Level and MCP-1 -2518 A/G and CCR2 190 G/A Gene Polymorphisms with COPD and Pulmonary Hypertension
Abstract
Objective: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by obstructed airflow in the lungs. Pulmonary hypertension (PH) is a common complication of COPD and it is associated with pulmonary vascular remodelling. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines associated with migration of monocytes and macrophages. Both MCP-1 and its receptor CCR2 have been declared to be involved in various diseases. We aimed to research a possible association of MCP-1 level, MCP-1 -2518 A/G and CCR2 190 A/G polymorphisms with COPD and pulmonary hypertension in this study.
Material and methods: Eighty patients and eighty controls were included in the study. Serum MCP-1 levels were measured by ELISA method. Restriction fragment length polymorphism (RFLP) procedure was used to detect the genotypes of patients and control group.
Results: MCP-1 levels were found to be significantly higher in COPD patients than in healthy controls (P=0.001) and patients with COPD + PH had higher serum MCP-1 levels than COPD patients (P=0.005). No association was found between MCP-1/CCR2 gene polymorphisms and patient groups (COPD and COPD + PH).
Conclusion: MCP-1 level seems to be associated with both COPD and pulmonary hypertension. Increased MCP-1 expression may most likely to be involved in the pathogenesis of these diseases.
References
Avci E, Avci GA. Important Biomarkers that Play a Role in the Chronic Obstructive Pulmonary Disease Process. J Med Biochem. 2018; 37: 46-53.
Yasui H, Inui N, Karayama M, Mori K, Hozumi H, Suzuki Y, et al. Correlation of the modified Medical Research Council dyspnea scale with airway structure assessed by three-dimensional CT in patients with chronic obstructive pulmonary disease. Respir Med. 2019; 146: 76-80.
Korytina GF, Akhmadishina LZ, Aznabaeva YG, Kochetova OV, Zagidullin NS, Kzhyshkowska JG, et al. Associations of the NRF2/KEAP1 pathway and antioxidant defense gene polymorphisms with chronic obstructive pulmonary disease. Gene. 2019; 692: 102-12.
Walczak A, Przybyłowska-Sygut K, Sygut A, Cieślak A, Mik M, Dziki Ł, et al. An association of the MCP-1 and CCR2 single nucleotide polymorphisms with colorectal cancer prevalence. Pol Przegl Chir. 2017; 89: 1-5.
Dutta P, Sarkissyan M, Paico K, Wu Y, Vadgama JV. MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis. Breast Cancer Res Treat. 2018; 170: 477-86.
Taghavi Y, Hassanshahi G, Kounis NG, Koniari I, Khorramdelazad H. Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy: latest evidence and clinical considerations. J Cell Commun Signal. 2019. doi: 10.1007/s12079-018-00500-8.
Li H, Li H, Li XP, Zou H, Liu L, Liu W, et al. C C chemokine receptor type 2 promotes epithelial to mesenchymal transition by upregulating matrix metalloproteinase 2 in human liver cancer. Oncol Rep. 2018; 40: 2734-41.
Frankenberger M, Eder C, Hofer TP, Heimbeck I, Skokann K, Kassner G, et al. Chemokine expression by small sputum macrophages in COPD. Mol Med. 2011; 17: 762-70.
Blidberg K, Palmberg L, Dahlén B, Lantz AS, Larsson K. Chemokine release by neutrophils in chronic obstructive pulmonary disease. Innate Immun. 2012; 18: 503-10.
Bracke KR, Demedts IK, Joos GF, Brusselle GG. CC-chemokine receptors in chronic obstructive pulmonary disease. Inflamm Allergy Drug Targets. 2007; 6: 75-9.
Miotla Zarebska J, Chanalaris A, Driscoll C, Burleigh A, Miller RE, Malfait AM, et al. CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy. Osteoarthritis Cartilage. 2017;25(3):406-12.
Bai J, Song H, Cai C, Zhang M, Xu S, Tan J. The association of monocyte chemotactic protein-1 and CC chemokine receptor 2 gene variants with chronic obstructive pulmonary disease. DNA Cell Biol. 2012; 31: 1058-63.
Schober A, Zernecke A. Chemokines in vascular remodeling. Thromb Haemost. 2007; 97: 730-7.
Park HJ, Lee SM, Choe J, Lee SM, Kim N, Lee JS, et al. Prediction of Treatment Response in Patients with Chronic Obstructive Pulmonary Disease by Determination of Airway Dimensions with Baseline Computed Tomography. Korean J Radiol. 2019; 20: 304-12.
Kyomoto Y, Kanazawa H, Tochino Y, Watanabe T, Asai K, Kawaguchi T. Possible role of airway microvascular permeability on airway obstruction in patients with chronicobstructive pulmonary disease. Respir Med. 2019; 146: 137-41.
Aldonyte R, Eriksson S, Piitulainen E, Wallmark A, Janciauskiene S. Analysis of systemic biomarkers in COPD patients. COPD. 2004; 1: 155-64.
Di Stefano A, Coccini T, Roda E, Signorini C, Balbi B, Brunetti G, et al. Blood MCP-1 levels are increased in chronic obstructive pulmonary disease patients with prevalent emphysema. Int J Chron Obstruct Pulmon Dis. 2018; 13: 1691-1700.
Yan C, Li B, Liu X, Deng C, Cai R, Shen Y, et al. Involvement of multiple transcription factors in regulation of IL-β-induced MCP-1 expression in alveolar type II epithelial cells. Mol Immunol. 2019 Apr 29; 111: 95-105.
Wang Y, Zheng Y, Zhai YL, Liu FQ, Ding N. Comparative analysis of MCP-1 and TF in elderly patients with acute exacerbations of COPD and its clinical significance. Eur Rev Med Pharmacol Sci. 2015; 19: 215-9.
Eickmeier O, Huebner M, Herrmann E, Zissler U, Rosewich M, Baer PC, et al. Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease(COPD) and association between pulmonary function. Cytokine. 2010; 50: 152-7.
Edmiston JS, Archer KJ, Scian MJ, Joyce AR, Zedler BK, Murrelle EL. Gene expression profiling of peripheral blood leukocytes identifies potential novel biomarkers of chronic obstructive pulmonary disease in current and former smokers. Biomarkers. 2010; 15: 715-30.
Wang Y, Zhang XA, Yang X, Wu ZH, Feng ZC. A MCP-1 promoter polymorphism at G-2518A is associated with spontaneous preterm birth. Mol Genet Genomics. 2015; 290: 289-96.
Mao B, Zhang J, Zhuo F. MCP-1-2518A>G polymorphism and myocardial infarction risk: a meta-analysis and meta-regression. Genet Test Mol Biomarkers. 2013; 17: 857-63.
Yildirim G, Attar R, Gulec-Yilmaz S, Duman S, Isbir T. Association of CCR2 (+190 G/A) Gene Variants and Ovarian Cancer Severity. Genet Test Mol Biomarkers. 2017; 21: 512-5.
Ben-Selma W, Harizi H, Boukadida J. MCP-1 -2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients. Mol Biol Rep. 2011; 38: 5413-9.
Liu SF, Wang CC, Fang WF, Chen YC, Lin MC. MCP1 -2518 polymorphism and chronic obstructive pulmonary disease in Taiwanese men. Exp Lung Res. 2010; 36: 277-83.
Schlosser K, Taha M, Deng Y, Jiang B, McIntyre LA, Mei SH, et al. Lack of elevation in plasma levels of pro-inflammatory cytokines in common rodent models of pulmonary arterial hypertension: questions of construct validity for human patients. Pulm Circ. 2017; 7: 476-85.
Amsellem V, Abid S, Poupel L, Parpaleix A, Rodero M, Gary-Bobo G, et al. Roles for the CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine Systems in Hypoxic Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2017; 56: 597-608.
