Genetic Polymorphisms in VEGFR Coding Genes (FLT1/KDR) on Ranibizumab Response in High Myopia and Choroidal Neovascularization Patients

Abstract

A severe form of myopia defined as pathologic/high myopia is the main cause of visual impairment and one of the most frequent causes of blindness worldwide. It is characterized by at least 6 diopters or axial length (AL) of eyeball >26 mm and choroidal neovascularization (CNV) in 5 to 10% of cases. Ranibizumab is a humanized recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A (VEGF-A) used in the treatment of CNV. It acts by preventing VEGF-A from interacting with its receptors (VEGFR-1 and -2) encoded by the FLT1 and KDR genes. Several studies found that the KDR and FLT1 genotypes may represent predictive determinants of efficacy in ranibizumab-treated neovascular age-related macular degeneration (nAMD) patients. We performed a retrospective study to evaluate the association of single nucleotide polymorphisms (SNPs) in VEGFR coding genes with the response rate to ranibizumab in patients with high myopia and CNV. In the association study of genotypes in FLT1 with the response to ranibizumab, we found a significant association between two FLT1 variants (rs9582036, rs7993418) with ranibizumab efficacy at the 12-month follow-up. About the KDR gene, we found that two KDR variants (rs2305948, rs2071559) are associated with best-corrected visual acuity (BCVA) improvement and KDR (rs2239702) is associated with lower rates of BCVA worsening considering a 12-month follow-up period.

Are Genetic Modifiers the Answer to Different Responses to Hydroxyurea Treatment?—A Pharmacogenetic Study in Sickle Cell Anemia Angolan Children

“…Ma et al had already identified in 2007 that five SNPs in this gene were associated with significant changes in HbF (% and g/dL) [14]. Previous studies have already found significant associations with this specific variant (rs7993418) and the response to ranibizumab [28,29].…”

Contribution of genetic polymorphism in ABCB1 to individual variations of imatinib plasma levels in patients with gastrointestinal stromal tumor

“…SNP in the metabolizing genes ( CYP3A4 , CYP3A5 , CYP2B6 , POR , and NR1I2 ) and the transporter family genes ( SLC22 , SLC19 , SLCO , and ABC ) were genotyped with an SNP mass array platform. Angiogenesis-related genes ( VEGFA , VEGFR2/KDR ), cytokine receptor gene ( IL4R ), and epidermal growth factor receptor gene ( EGFR ) were also analyzed ( 12 - 14 ). We present this article in accordance with the REMARK reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-188/rc ).…”

Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor

“…Although anti-vascular endothelial growth factor (VEGF) therapy has replaced photodynamic therapy, pmCNV remains an urgent challenge for low responders and a burden for patients who need multiple treatments or among patients with severe myopic maculopathy [5,6]. Remarkably, the efficacy of anti-VEGF drugs, such as ranibizumab, may depend on genetic polymorphisms, in which FLT1 (rs9582036, rs7993418) variants may serve as a genetic marker [7]. In fact, other risk factor, including the presence of perforating scleral vessels or macular Bruch membrane breakdown, may hinder the response to anti-VEGF therapy as well [8,9].…”