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Title: Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies
Authors: Gareth J. Mckay
Chris C. Patterson
Usha Chakravarthy
Shilpa Dasari
Caroline C. Klaver
Johannes R. Vingerling
Lintje Ho
Paulus T.V.M. de Jong
Astrid E. Fletcher
Ian S. Young
Johan H. Seland
Mati Rahu
Gisele Soubrane
Laura Tomazzoli
Fotis Topouzis
Jesus Vioque
Aroon D. Hingorani
Reecha Sofat
Michael Dean
Julie Sawitzke
Johanna M. Seddon
Inga Peter
Andrew R. Webster
Anthony T. Moore
John R.W. Yates
Valentina Cipriani
Lars G. Fritsche
Bernhard H.F. Weber
Claudia N. Keilhauer
Andrew J. Lotery
Sarah Ennis
Michael L. Klein
Peter J. Francis
Dwight Stambolian
Anton Orlin
Michael B. Gorin
Daniel E. Weeks
Chia Ling Kuo
Anand Swaroop
Mohammad Othman
Atsuhiro Kanda
Wei Chen
Goncalo R. Abecasis
Alan F. Wright
Caroline Hayward
Paul N. Baird
Robyn H. Guymer
John Attia
Ammarin Thakkinstian
Giuliana Silvestri
Queen's University Belfast
Erasmus University Medical Center
Netherlands Institute for Neuroscience NIN - KNAW
Academic Medical Centre, University of Amsterdam
London School of Hygiene & Tropical Medicine
Stavanger University Hospital
Tervise Arengu Instituut
Universitaire de Creteil
Clinica Oculistica
Aristotle University of Thessaloniki
Universidad Miguel Hernandez de Elche
National Cancer Institute at Frederick
Tufts University School of Medicine
Tufts Medical Center
Icahn School of Medicine at Mount Sinai
UCL Institute of Ophthalmology
Moorfields Eye Hospital NHS Foundation Trust
University of Cambridge
Universitat Regensburg
Universitatsklinikum Wurzburg
University of Southampton
Southampton General Hospital
OHSU School of Medicine
University of Pennsylvania
David Geffen School of Medicine at UCLA
University of Pittsburgh Graduate School of Public Health
The University of the Michigan Kellogg Eye Center
National Eye Institute
University of Michigan School of Public Health
Western General Hospital
University of Melbourne
University of Newcastle, Australia
John Hunter Hospital
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-Dec-2011
Citation: Human Mutation. Vol.32, No.12 (2011), 1407-1416
Abstract: Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI] : 0.65-0.74; P = 4.41×10 -11 ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10 -15 ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10 -5 ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. © 2011 Wiley Periodicals, Inc.
ISSN: 10981004
Appears in Collections:Scopus 2011-2015

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