Evidence of association ofAPOEwith age-related macular degeneration - a pooled analysis of 15 studies
- 31 August 2011
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 32 (12), 1407-1416
- https://doi.org/10.1002/humu.21577
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. 32:1407–1416, 2011. ©2011 Wiley Periodicals, Inc.Keywords
This publication has 75 references indexed in Scilit:
- Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older PeopleAmerican Journal of Epidemiology, 2011
- Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degenerationProceedings of the National Academy of Sciences of the United States of America, 2010
- Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene ( LIPC )Proceedings of the National Academy of Sciences of the United States of America, 2010
- Multilocus analysis of age-related macular degenerationEuropean Journal of Human Genetics, 2009
- Variation near complement factor I is associated with risk of advanced AMDEuropean Journal of Human Genetics, 2008
- A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degenerationProceedings of the National Academy of Sciences of the United States of America, 2007
- Variation in complement factor 3 is associated with risk of age-related macular degenerationNature Genetics, 2007
- An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulationEnvironmental and Molecular Mutagenesis, 2006
- Does smoking influence the type of age related macular degeneration causing visual impairment?British Journal of Ophthalmology, 2006
- Complement Factor H Polymorphism in Age-Related Macular DegenerationScience, 2005