Common variant in VEGFA and response to anti-VEGF therapy for neovascular age-related macular degeneration.

Abstract

Age-related macular degeneration (AMD) is a leading cause of visual impairment in aging populations in industrialized countries. Here we investigated whether the genotype of vascular endothelial growth factor A (VEGFA) gene is associated with response to anti-VEGF therapy. 223 eyes with neovascular AMD were treated with intravitreal anti-VEGF therapy. Responders were defined as patients who had an improvement in best corrected visual acuity (BCVA) of at least 5 letters or one line on the EDTRS visual acuity chart along with resolution of intraretinal or subretinal fluid over 12 months. Patients who did not meet the definition of responders were classified as poor-responders. The vision of responders (n = 148) improved while the vision of poor-responders (n = 75) worsened (P<0.001). Responders on average had a decrease in central foveal thickness (CFT), while poor-responders had an increase in CFT (P <0.001). Compared with the responder group, the poor-responder group had a higher frequency of the risk (T) allele (Allelic P = 0.019) and TT genotype (P = 0.002 under a recessive model) for the VEGFA-rs943080 polymorphism. VEGFA expression was 1.8-fold higher in cells with the VEGFA rs943080 TT genotype than in cells with the VEGFA rs943080 CC genotype (P = 0.012). Age, gender, smoking, diabetes mellitus, and hypertension did not play a significant role in treatment response, but BMI was found to be significantly different between responders and poorresponders (P = 0.033). In conclusion, we demonstrated a potential pharmacogenetic relationship between the VEGFA gene and treatment response to anti-VEGF therapy.The studies are registered at ClinicalTrials.gov under the identifiers NCT00474695 (http://clinicaltrials. gov/ct2/show/NCT00474695) and NCT01464723 (http://clinicaltrials.gov/ct2/show/NCT01464723).

• Authors: L Zhao, S Grob, R Avery, A Kimura, D Pieramici, J Lee, M Rabena, S Ortiz, J Quach, G Cao, H Luo, M Zhang, M Pei, Y Song, P Tornambe, M Goldbaum, H Ferreyra, I Kozak, K Zhang
• Journal: Current molecular medicine (Curr Mol Med) Vol. 13 Issue 6 Pg. 929-34 (Jul 2013) ISSN: 1875-5666 [Electronic] Netherlands
• PMID: 23745581 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal, Humanized
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Bevacizumab
• Ranibizumab

Topics

• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Bevacizumab
• Demography
• Female
• Gene Expression Regulation (drug effects)
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Lymphocytes (drug effects, metabolism)
• Male
• Polymorphism, Single Nucleotide (genetics)
• Ranibizumab
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, genetics)
• Wet Macular Degeneration (drug therapy, genetics)