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      Association between Apolipoprotein ε4 Gene Polymorphism and Risk of Ischemic Stroke: A Meta-Analysis

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          Background: Previous studies examining the association of apolipoprotein E (APOE) gene polymorphism with the risk of ischemic stroke (IS) have yielded conflicting results. Therefore, we performed a meta-analysis to investigate the association between APOE ε4 gene polymorphism and risk of IS. Summary: A literature search for genetic association studies published before May 30, 2015, was conducted in the PubMed, EMBASE and Google Scholar databases. The following search terms were used: (apolipoprotein E) or (APOE) and (ε4) and (polymorphism) or (polymorphisms) and (‘ischemic stroke' or ‘IS') and (‘cerebral infarction' or ‘CI') and (‘genetic polymorphism' or ‘single nucleotide polymorphisms' or ‘SNP'). ORs and 95% CIs were used to calculate the strength of association. Begg's funnel plot was used to assess the potential for publication bias. In our meta-analysis, 26 case-control studies involving 6,397 IS cases and 19,053 controls were included. Overall significant association between carrier of ε4 allele and risk of IS was observed (OR 1.43, 95% CI 1.10-1.85, p = 0.007). In the subgroup analysis based on ethnicity, a significant association between Apo ε4 carrier and risk of IS was observed in Asian studies (OR 1.53, 95% CI 1.04-2.25, p = 0.031) whereas borderline significant association between APO ε4 carrier and risk of IS was observed in Caucasian studies (OR 1.36, 95% CI 0.95-1.93, p = 0.093). Key Messages: Our meta-analysis suggests that APOE ε4 allele is associated with higher risk of IS in Asian population as compared to Caucasian population.

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          Most cited references 24

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          Measuring inconsistency in meta-analyses.

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            Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review.

            This systematic review of population-based studies of the incidence and early (21 days to 1 month) case fatality of stroke is based on studies published from 1970 to 2008. Stroke incidence (incident strokes only) and case fatality from 21 days to 1 month post-stroke were analysed by four decades of study, two country income groups (high-income countries and low to middle income countries, in accordance with the World Bank's country classification) and, when possible, by stroke pathological type: ischaemic stroke, primary intracerebral haemorrhage, and subarachnoid haemorrhage. This Review shows a divergent, statistically significant trend in stroke incidence rates over the past four decades, with a 42% decrease in stroke incidence in high-income countries and a greater than 100% increase in stroke incidence in low to middle income countries. In 2000-08, the overall stroke incidence rates in low to middle income countries have, for the first time, exceeded the level of stroke incidence seen in high-income countries, by 20%. The time to decide whether or not stroke is an issue that should be on the governmental agenda in low to middle income countries has now passed. Now is the time for action.
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              Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.

               R Mahley (1988)
              Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body. A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease. Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol. Apolipo-protein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration. Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation.

                Author and article information

                Annals of Neurosciences
                Ann Neurosci
                S. Karger AG (Basel, Switzerland karger@ )
                July 2016
                07 July 2016
                : 23
                : 2
                : 113-121
                Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
                AON2016023002113 PMC5020389 Ann Neurosci 2016;23:113-121
                © 2016 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 2, References: 42, Pages: 9
                Mini Review


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