Publication:
Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

Issued Date

2011-12-01

Resource Type

Article

ISSN

10981004
10597794

DOI

10.1002/humu.21577

Other identifier(s)

2-s2.0-81255168210

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Human Mutation. Vol.32, No.12 (2011), 1407-1416

Suggested Citation

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 Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies. Human Mutation. Vol.32, No.12 (2011), 1407-1416. doi:10.1002/humu.21577 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/11425

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Title

Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

Author(s)

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

Other Contributor(s)

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
 CIBERESP
 UCL
 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

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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/11425

Collections

Scopus 2011-2015