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      Myeloperoxidase polymorphism and coronary artery disease risk : A meta-analysis

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          Abstract

          The myeloperoxidase ( MPO) gene 463G/A and 129G/A polymorphisms have been reported to be associated with coronary artery disease (CAD), but the results remain inconclusive. This meta-analysis was designed to clarify these controversies.

          PubMed, EMBASE, and the Cochrane Library were used to retrieve the relevant literature up to March 2015 according to keywords. A total of 8 case–control studies, including 3491 cases and 7293 controls, were included in this meta-analysis. Summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated.

          There was strong evidence of an association between the MPO 463G/A polymorphism and CAD. The data revealed that only the dominant model was associated with CAD (dominant model: OR = 0.872, 95% CI = 0.77–0.99). Regarding the 129G/A gene polymorphism, the pooled OR for the genotype AA + AG versus GG was 0.906 (95% CI = 0.74–1.10).

          This meta-analysis suggested an association between the MPO 463G/A polymorphism and the risk of CAD, but there is no significant association between the MPO 129G/A gene polymorphism and CAD risk.

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          Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes.

          Stephan Baldus, Christopher Heeschen, Thomas Meinertz … (2003)
          Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown. MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (>350 microg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P=0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 microg/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P=0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P=0.023), C-reactive protein (1.25; P=0.044), vascular endothelial growth factor (HR 1.87; P=0.041), soluble CD40 ligand (HR 2.78; P<0.001), and MPO (HR 2.11; P=0.008) were all independent predictors of the patient's 6-month outcome. In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS.
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            Myeloperoxidase and cardiovascular disease.

            Stephen Nicholls, Stanley Hazen (2005)
            Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species. In addition to being an integral component of the innate immune response, evidence has emerged that MPO-derived oxidants contribute to tissue damage during inflammation. MPO-catalyzed reactions have been attributed to potentially proatherogenic biological activities throughout the evolution of cardiovascular disease, including during initiation, propagation, and acute complication phases of the atherosclerotic process. As a result, MPO and its downstream inflammatory pathways represent attractive targets for both prognostication and therapeutic intervention in the prophylaxis of atherosclerotic cardiovascular disease.
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              Association between myeloperoxidase levels and risk of coronary artery disease.

              R. Zhang, Stanley Hazen, John S. Penn … (2001)
              Myeloperoxidase (MPO), a leukocyte enzyme that promotes oxidation of lipoproteins in atheroma, has been proposed as a possible mediator of atherosclerosis. To determine the association between MPO levels and prevalence of coronary artery disease (CAD). Case-control study conducted from July to September 2000 in a US tertiary care referral center, including 158 patients with established CAD (cases) and 175 patients without angiographically significant CAD (controls). Association of MPO levels per milligram of neutrophil protein (leukocyte-MPO) and MPO levels per milliliter of blood (blood-MPO) with CAD risk. Leukocyte- and blood-MPO levels were both significantly greater in patients with CAD than in controls (P<.001). In multivariable models adjusting for traditional cardiovascular risk factors, Framingham risk score, and white blood cell counts, MPO levels were significantly associated with presence of CAD, with an OR of 11.9 (95% CI, 5.5-25.5) for the highest vs lowest quartiles of leukocyte-MPO and an OR of 20.4 (95% CI, 8.9-47.2) for the highest vs lowest quartiles of blood-MPO. Elevated levels of leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: July 2017
                Publication date (Electronic): 07 July 2017
                Volume: 96
                Issue: 27
                Electronic Location Identifier: e7280
                Affiliations
                [a ]Department of Emergency
                [b ]Department of Intensive Care Unit, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
                Author notes
                [∗ ]Correspondence: Xiang-Yang Zhang, Department of Emergency, Beijing Tsinghua Changgung Hospital, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, China (e-mail: aazxy@ 123456sina.com )
                Article
                Publisher ID: MD-D-17-00428 Accession ID: 07280
                DOI: 10.1097/MD.0000000000007280
                PMC ID: 5502150
                PubMed ID: 28682877
                SO-VID: 70afdf39-4325-4a0a-a1da-bfc56338726d
                Copyright © Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                Date received : 19 January 2017
                Date revision received : 30 May 2017
                Date accepted : 5 June 2017
                Categories
                Subject: 3400
                Subject: Research Article
                Subject: Meta-Analysis of Observational Studies in Epidemiology
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: coronary artery disease,meta-analysis,myeloperoxidase,polymorphism
                Data availability:
                Keywords: coronary artery disease, meta-analysis, myeloperoxidase, polymorphism

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