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      The Apolipoprotein E ε4 Allele Is Unlikely to Be a Major Risk Factor of Age-Related Macular Degeneration in Chinese

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          Abstract

          Apolipoprotein E (ApoE) is a major transporter of lipids and cholesterol in the nervous system. Age-related macular degeneration (ARMD), characterized by drusen containing lipids, was reported to show a lower frequency of the ApoE ε4 allele than control subjects. We sought to examine the association of this polymorphism with ARMD in Hong Kong Chinese. Among 98 ARMD subjects, the frequency of ε4 carriers showed a trend toward a decrease compared to controls, but it was not significant (11.2 vs. 15.0%, p < 0.52). The association of ε4 with an apparent reduced risk of ARMD was reported previously in the exudative form of the disease, however among 39 exudative ARMD patients there was also no significant difference in ε4 frequency (12.8%, p < 0.93). The lack of a statistically significant effect of ε4 may be due to the lower frequency of ε4 in Chinese than Europeans. Thus we cannot exclude a possible effect of this allele on ARMD risk, but we can conclude that this allele is likely not a major factor influencing ARMD risk in the Chinese.

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          Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration.

          Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in ABCR, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of ABCR in 26 patients (16%). Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy.
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            Genetic association of apolipoprotein E with age-related macular degeneration.

            Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic-association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam Study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2. 82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.
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              Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration.

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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                0030-3755
                1423-0267
                2000
                August 2000
                07 June 2000
                : 214
                : 4
                : 289-291
                Affiliations
                Departments of aOphthalmology and Visual Sciences and bChemical Pathology, Chinese University of Hong Kong, Hong Kong
                Article
                27506 Ophthalmologica 2000;214:289–291
                10.1159/000027506
                10859513
                © 2000 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Tables: 1, References: 17, Pages: 3
                Categories
                Original Paper · Travail original · Originalarbeit

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