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      Meta-Analysis of Factor V, Factor VII, Factor XII, and Factor XIII-A Gene Polymorphisms and Ischemic Stroke

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          Abstract

          Background and aims: Numerous studies examined the association between factors FV, FVII, FXII, and FXIII-A gene polymorphisms and ischemic stroke, but conclusive evidence is yet to be obtained. Thus, this meta-analysis aimed to investigate the novel association of FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms with ischemic stroke risk. Methods: A systematic review was performed on articles retrieved before June 2018. Relevant data were extracted from eligible studies and meta-analyzed using RevMan version 5.3. The strength of association between studied polymorphisms and ischemic stroke risk was calculated as odds ratios and 95% confidence intervals, by applying both fixed- and random-effect models. Results: A total of 25 studies involving 6100 ischemic stroke patients and 9249 healthy controls were incorporated in the final meta-analysis model. Specifically, rs1800595, rs5742910, rs1801020, rs5982, and rs3024477 consisted of 673, 3668, 922, 433, and 404 cases, as well as 995, 4331, 1285, 1321, and 1317 controls, respectively. The pooled analysis indicated that there was no significant association of FV rs1800595, FVII rs5742910, FXII rs1801020, FXIII-A rs5982, and FXIII-A rs3024477 polymorphisms with ischemic stroke risk, under any genetic models (dominant, recessive, over-dominant, and allelic). Conclusions: The present meta-analysis concluded that FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms are not associated with ischemic stroke risk.

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          Metabolomics and Lipidomics of Ischemic Stroke.

          Anthony Au (2018)
          Ischemic stroke is a sudden loss of brain function due to the reduction of blood flow. Brain tissues cease to function with subsequent activation of the ischemic cascade. Metabolomics and lipidomics are modern disciplines that characterize the metabolites and lipid components of a biological system, respectively. Because the pathogenesis of ischemic stroke is heterogeneous and multifactorial, it is crucial to establish comprehensive metabolomic and lipidomic approaches to elucidate these alterations in this disease. Fortunately, metabolomic and lipidomic studies have the distinct advantages of identifying tissue/mechanism-specific biomarkers, predicting treatment and clinical outcome, and improving our understanding of the pathophysiologic basis of disease states. Therefore, recent applications of these analytical approaches in the early diagnosis of ischemic stroke were discussed. In addition, the emerging roles of metabolomics and lipidomics on ischemic stroke were summarized, in order to gain new insights into the mechanisms underlying ischemic stroke and in the search for novel metabolite biomarkers and their related pathways.
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            Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis.

            The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies.
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              Novel Hemostatic Factor Levels and Risk of Ischemic Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

              Background and Objective: The role of hemostatic factor levels in cerebral infarction remains uncertain. We studied the association of levels of several under-studied hemostatic factors with ischemic stroke in a population-based cohort. Methods: The Atherosclerosis Risk in Communities (ARIC) study includes 15,792 individuals aged 45–54 years at intake. Hemostatic factors II, V, IX, X, XI, XII, plasminogen and α 2 -antiplasmin were measured on frozen citrate plasma samples from 1990 to 1992. A case-cohort design was used, including all incident ischemic strokes (n = 89) over a median of 7.5 years and a stratified cohort random sample (n = 412). To determine the association of hemostatic factors with incident ischemic stroke, we computed hazard ratios (HRs) using multivariate proportional hazard regression analyses adjusted for demographic and other cardiovascular risk factors. Results: The cohort random sample had a mean age (SD) of 56.9 (5.4) years and 42% were men. The age-, sex- and race-adjusted HRs for highest versus lowest quartiles were: factor XI (2.74, 95% CI 1.42–5.29), factor IX (1.92, 95% CI 0.99–3.73), and α 2 -antiplasmin (2.24, 95% CI 1.16–4.33). Correspondingly, the HRs of ischemic stroke per SD increment of factors XI, IX, and α 2 -antiplasmin were 1.64, 1.46 and 1.52, respectively (all p < 0.05). After multivariate adjustment including other clinical variables, the standardized HR remained significant for factor XI (1.50, 95% CI 1.10–2.05), but no other factor. Conclusion: A greater level of factor XI was associated with an increased risk of ischemic stroke. Higher factor XI levels might help identify patients at elevated ischemic stroke risk.
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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                11 April 2019
                April 2019
                : 55
                : 4
                : 101
                Affiliations
                [1 ]Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Bandar Barat, Kampar 31900, Perak, Malaysia
                [2 ]Genomics Research Centre, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Musk Avenue, Kelvin Grove QLD 4059, Australia; lyn.griffiths@ 123456qut.edu.au
                [3 ]Department of Medicine and Clinical Research Centre, Hospital Taiping, Jalan Tamingsari, Taiping 34000, Perak, Malaysia; wkcheah@ 123456hotmail.com
                [4 ]Department of Medicine and Clinical Research Centre, Hospital Seberang Jaya, Jalan Tun Hussein Onn, Seberang Jaya 13700, Pulau Pinang, Malaysia; irenelooi@ 123456yahoo.com
                Author notes
                [* ]Correspondence: wynnelkw@ 123456gmail.com
                Author information
                https://orcid.org/0000-0003-1853-0352
                https://orcid.org/0000-0002-6774-5475
                Article
                medicina-55-00101
                10.3390/medicina55040101
                6524011
                30979054
                066daae4-09d2-4f4c-af37-1d9243c7287e
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 March 2019
                : 04 April 2019
                Categories
                Article

                meta-analysis,fv,fvii,fxii,fxiii-a,polymorphisms,ischemic stroke,coagulation cascade

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