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


McKay, GJ; Patterson, CC; Chakravarthy, U; Dasari, S; Klaver, CC; Vingerling, JR; Ho, L; de Jong, PT; Fletcher, AE; Young, IS; Seland, JH; Rahu, M; Soubrane, G; Tomazzoli, L; Topouzis, F; Vioque, J; Hingorani, AD; Sofat, R; Dean, M; Sawitzke, J; Seddon, JM; Peter, I; Webster, AR; Moore, AT; Yates, JR; Cipriani, V; Fritsche, LG; Weber, BH; Keilhauer, CN; Lotery, AJ; Ennis, S; Klein, ML; Francis, PJ; Stambolian, D; Orlin, A; Gorin, MB; Weeks, DE; Kuo, CL; Swaroop, A; Othman, M; Kanda, A; Chen, W; Abecasis, GR; Wright, AF; Hayward, C; Baird, PN; Guymer, RH; Attia, J; Thakkinstian, A; Silvestri, G; (2011) Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies. Human mutation, 32 (12). pp. 1407-16. ISSN 1059-7794 DOI: https://doi.org/10.1002/humu.21577

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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 APO?4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APO?2 (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 ?2 and ?4 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 21882290
Web of Science ID: 297246800013
URI: http://researchonline.lshtm.ac.uk/id/eprint/60

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