Polymorphisms in the Vascular Endothelial Growth Factor Gene and Risk of Age-related Macular Degeneration: The Rotterdam Study
Received 6 January 2008; received in revised form 25 May 2008; accepted 20 June 2008. published online 19 August 2008.
Purpose
Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and a target for inhibition therapy in wet age-related macular degeneration (AMD). The purpose of this study was to examine whether genetic variation in the VEGF gene is associated with AMD and, especially, with its wet end stage.
Design
Prospective population-based cohort study.
Participants
Four thousand two hundred twenty-eight participants aged 55 years and older.
Methods
AMD was classified according to a modified International Classification System using fundus color images. Genotypes and haplotypes were determined for 3 functional VEGF single nucleotide polymorphisms (SNPs): C-2578A, G-1154A, and G-634C. Cox proportional hazards regression analyses were used to investigate possible associations between the individual SNPs and incident AMD. The Haplo.Stats program was used to test the associations between VEGF gene haplotypes and incident AMD.
Main Outcome Measure
AMD
Results
Of 4228 participants at risk for incident early and late AMD for whom blood specimens were available for VEGF genotyping, incident early AMD developed in 514 and incident late AMD developed in 89 (35 dry and 54 wet) after a mean follow-up of 7.4 years. None of the SNPs showed a significant association with incident early or late AMD, especially not with incident wet AMD. Haplotype analyses also detected no associations.
Conclusions
The a priori hypothesis that 3 common SNPs in the VEGF gene would be a risk factor for AMD, especially the wet form, could not be confirmed.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found after the references.
Available online: August 16, 2008.
1Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
2Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
3The Netherlands Institute for Neuroscience, KNAW, Amsterdam, The Netherlands
4Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands
5Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands
Correspondence: Johannes R. Vingerling, MD, PhD, P. O. Box 2040, 3000 CA Rotterdam, The Netherlands
Manuscript no. 2008-35.
Financial Disclosure(s): The funding sources had no involvement in the authors' work.
Supported by The Netherlands Organization for Scientific Research (NWO), The Hague, The Netherlands; Optimix, Amsterdam, The Netherlands; Physico Therapeutic Institute, Rotterdam, The Netherlands; Blindenpenning, Amsterdam, The Netherlands; Sint Laurens Institute, Rotterdam, The Netherlands; Bevordering van Volkskracht, Rotterdam, The Netherlands; Blindenhulp, The Hague, The Netherlands; Rotterdamse Blindenbelangen Association, Rotterdam, The Netherlands; OOG, The Hague, The Netherlands; kfHein, Utrecht, The Netherlands; Prins Bernhard Cultuurfonds, Amsterdam, The Netherlands; Van Leeuwen Van Lignac, Rotterdam, The Netherlands; Verhagen, Rotterdam, The Netherlands; and Elise Mathilde, Maarn, The Netherlands. An unrestricted grant was obtained from Topcon Europe BV, Capelle aan de IJssel; all in The Netherlands.
ABSTRACT