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Evidence of association of APOE with age‐related macular degeneration ‐ a pooled analysis of 15 studies
Author(s) -
McKay Gareth J.,
Patterson Chris C.,
Chakravarthy Usha,
Dasari Shilpa,
Klaver Caroline C.,
Vingerling Johannes R.,
Ho Lintje,
de Jong Paulus T.V.M.,
Fletcher Astrid E.,
Young Ian S.,
Seland Johan H.,
Rahu Mati,
Soubrane Gisele,
Tomazzoli Laura,
Topouzis Fotis,
Vioque Jesus,
Hingorani Aroon D.,
Sofat Reecha,
Dean Michael,
Sawitzke Julie,
Seddon Johanna M.,
Peter Inga,
Webster Andrew R.,
Moore Anthony T.,
Yates John R.W.,
Cipriani Valentina,
Fritsche Lars G.,
Weber Bernhard H.F.,
Keilhauer Claudia N.,
Lotery Andrew J.,
Ennis Sarah,
Klein Michael L.,
Francis Peter J.,
Stambolian Dwight,
Orlin Anton,
Gorin Michael B.,
Weeks Daniel E.,
Kuo ChiaLing,
Swaroop Anand,
Othman Mohammad,
Kanda Atsuhiro,
Chen Wei,
Abecasis Goncalo R.,
Wright Alan F.,
Hayward Caroline,
Baird Paul N.,
Guymer Robyn H.,
Attia John,
Thakkinstian Ammarin,
Silvestri Giuliana
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21577
Subject(s) - macular degeneration , apolipoprotein e , odds ratio , haplotype , medicine , confidence interval , biology , etiology , cholesterol , disease , risk factor , genotype , genetics , ophthalmology , gene
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. 32:1407–1416, 2011. ©2011 Wiley Periodicals, Inc.