Polymorphisms in the vascular endothelial growth factor gene and risk of age-related macular degeneration: the Rotterdam Study.
OBJECTIVE
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.


METHODS
Prospective population-based cohort study.


METHODS
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.


METHODS
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.
Boekhoorn
Sharmila S
SS
Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Isaacs
Aaron
A
Uitterlinden
André G
AG
van Duijn
Cornelia M
CM
Hofman
Albert
A
de Jong
Paulus T V M
PT
Vingerling
Johannes R
JR
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A