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Polymorphic variations affecting response to anti‐VEGF therapy in patients with exudative age‐related macular degeneration
Author(s) -
Wang Vinson Matthew,
Rosen Richard,
Meyerle Catherine,
Kurup Shree,
Chew Emily,
Chan ChiChao,
Tuo Jingsheng
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.969.3
Subject(s) - macular degeneration , ranibizumab , medicine , bevacizumab , pathogenesis , pharmacogenomics , vascular endothelial growth factor , cytokine , single nucleotide polymorphism , snp , oncology , biomarker , bioinformatics , vegf receptors , ophthalmology , genotype , pharmacology , gene , chemotherapy , biology , genetics
Age‐related macular degeneration (AMD) is the leading cause of central, irreversible visual impairment in the elderly and genetic components are major contributors to disease pathogenesis. The most widely utilized therapy option for neovascular AMD is intravitreal administration of anti‐vascular endothelial growth factor (VEGF) antibodies such as bevacizumab and ranibizumab. However, some AMD patients do not respond (continue to exhibit subretinal fluid or continue to loose visual acuity) adequately to this therapy. We hypothesized that a pharmacogenomic mechanism may play a role in the differentiated therapy response and examined 12 SNPs within CFH, HTRA1, IL‐17, IL‐23R, CYP3A, and LEP in 43 patients (29 responders and 14 non‐responders). We observed a higher rate of G allele carriers in the responders (4/29) compared to the non‐responders (0/14) for an IL‐23R SNP, rs11465804. In addition to examining genotypic variations, we also arrayed the expression of 36 cytokines in the plasma of selected responders/non‐responders using R&D Systems' Human Cytokine Array Panel A. We found that plasma IL‐17, a pro‐inflammatory cytokine regulated by IL‐23R, was higher in the non‐responders (n=1) than that of the responders (n=2). These results suggest that gene variation within IL‐23R and altered relevant cytokine profile might contribute to the distinct efficacy of anti‐VEGF therapy for exudative AMD.