Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies
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, Chia-Ling, 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 and Silvestri, Giuliana (2011) Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies. Human Mutation, 32, (12), 1407-1416. (doi:10.1002/humu.21577). (PMID:21882290).
Download
Full text not available from this repository.
Description/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.
| Item Type: | Article |
|---|---|
| ISSNs: | 1059-7794 (print) 1098-1004 (electronic) |
| Related URLs: | |
| Subjects: | Q Science > QH Natural history > QH426 Genetics |
| Divisions: | Faculty of Medicine > Human Development and Health Faculty of Medicine > Infection, Inflammation and Immunity |
| Item ID: | 337656 |
| Date Deposited: | 02 May 2012 09:04 |
| Last Modified: | 19 Jul 2012 13:29 |
| Contributors: | McKay, Gareth J. (Author) Patterson, Chris C. (Author) Chakravarthy, Usha (Author) Dasari, Shilpa (Author) Klaver, Caroline C. (Author) Vingerling, Johannes R. (Author) Ho, Lintje (Author) de Jong, Paulus T.V.M. (Author) Fletcher, Astrid E. (Author) Young, Ian S. (Author) Seland, Johan H. (Author) Rahu, Mati (Author) Soubrane, Gisele (Author) Tomazzoli, Laura (Author) Topouzis, Fotis (Author) Vioque, Jesus (Author) Hingorani, Aroon D. (Author) Sofat, Reecha (Author) Dean, Michael (Author) Sawitzke, Julie (Author) Seddon, Johanna M. (Author) Peter, Inga (Author) Webster, Andrew R. (Author) Moore, Anthony T. (Author) Yates, John R.W. (Author) Cipriani, Valentina (Author) Fritsche, Lars G. (Author) Weber, Bernhard H.F. (Author) Keilhauer, Claudia N. (Author) Lotery, Andrew J. (Author) Ennis, Sarah (Author) Klein, Michael L. (Author) Francis, Peter J. (Author) Stambolian, Dwight (Author) Orlin, Anton (Author) Gorin, Michael B. (Author) Weeks, Daniel E. (Author) Kuo, Chia-Ling (Author) Swaroop, Anand (Author) Othman, Mohammad (Author) Kanda, Atsuhiro (Author) Chen, Wei (Author) Abecasis, Goncalo R. (Author) Wright, Alan F. (Author) Hayward, Caroline (Author) Baird, Paul N. (Author) Guymer, Robyn H. (Author) Attia, John (Author) Thakkinstian, Ammarin (Author) Silvestri, Giuliana (Author) |
| Date: | December 2011 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/337656 |
Actions (login required)
 |
View Item |
