Vascular endothelial growth factor gene variation and the response to photodynamic therapy in age-related macular degeneration.
OBJECTIVE
To evaluate the role of vascular endothelial growth factor (VEGF) gene polymorphisms in exudative age-related macular degeneration (AMD).


METHODS
Retrospective, comparative case series.


METHODS
Patients with recent exudative AMD (n = 162) and age-matched subjects without AMD (n = 85).


METHODS
Fluorescein angiography (FA), clinical examination, and single nucleotide polymorphism (SNP) genotyping.


METHODS
The frequencies of 3 VEGF gene SNPs were analyzed, 1 at the promoter site (rs699947, A-->C) and 2 intronic SNPs (rs2146323, A-->C, and rs3025033, A-->G), in relation to the risk of AMD, to choroidal neovascular (CNV) lesion size and configuration, and to the anatomic response to photodynamic therapy (PDT). These SNPs were chosen to cover all the haploblocks of the VEGF gene. The 86 patients who had undergone PDT were classified as either PDT responders or PDT nonresponders based on the outcome of PDT after the last treatment session. For the PDT responders, the treating physician had deemed the lesion to be clinically dry and without leakage from CNV in FA at a visit scheduled at least 12 weeks after the last PDT treatment. For the PDT nonresponders, the PDT sessions had been discontinued by the treating retina specialist because of an apparently poor response and a still exudative lesion after several PDT sessions.


RESULTS
The presence of exudative AMD or lesion size or configuration was not associated with the SNPs studied here. The frequencies of the rs699947 were significantly different in PDT nonresponders and PDT responders. The AA, AC, and CC genotypes were 14%, 39%, and 46%, respectively, in PDT nonresponders, compared with 40%, 48%, and 12%, respectively, in the PDT responders (P = 0.0008). The corresponding frequencies for the rs2146323 AA, AC, and CC genotypes were 4%, 32%, and 64%, respectively, in nonresponders and 24%, 38%, and 38%, respectively, in responders (P = 0.0369). The genotypes of the rs3025033 SNP were distributed evenly between the responders and nonresponders.


CONCLUSIONS
The VEGF gene polymorphic SNPs at rs699947 and rs2146323 are strong determinants of the anatomic outcome after PDT, but the SNPs studied were not associated with the presence of exudative AMD or with the CNV lesion size or configuration.


BACKGROUND
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Immonen
Ilkka
I
Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland.
Seitsonen
Sanna
S
Tommila
Petri
P
Kangas-Kontio
Tiia
T
Kakko
Sakari
S
Savolainen
Eeva-Riitta
ER
Savolainen
Markku J
MJ
Liinamaa
M Johanna
MJ
D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D010778:Photochemotherapy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A