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

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 344 KB
• Volume: 32
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.21577

✦ Synopsis

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.