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Alvaro Velazquez Villoria, Sergio Recalde, Patricia Fernandez-Robredo, Carla Barreales, Esefanía Cobos, Alicia Valverde, Marta Suarez-Figueroa, Fernando Cruz, Maximino Abraldes, Alfredo Garcia Layana; Different Association of ARMS2, CFH, CFHR1-3, SERPINF1, VEGFR1 and C5 Polymorphisms in response of Ranibizumab treatment in wet-AMD.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3787.
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To determine if prespecified genetic single nucleotide polymorphisms (SNPs) influence responsiveness to vascular endothelial growth factor (VEGF) inhibition by Ranibizumab in neovascular age-related macular degeneration (AMD) in Spanish patients.
A cohort of 400 Caucasian patients with unilateral exudative AMD<br /> received intravitreal ranibizumab. After a three-injection loading phase, a PRN<br /> regimen was followed. Thirteen SNPs of 8 genes (CFH, CFHR1-3, CFB, ARMS2, C5, SERPINF1, VEGFR1, VEGF) were genotyped to evaluate their influence in the response to Ranibizumab. Non-genetic risk factors, (gender, smoking habit, and hypertension) were considered. The classification of good/bad responder was made using functional (visual acuity measured by ETDRS), anatomical (liquid/no liquid measured by OCT) and number of injections criteria. The genotyping was performed using multiplex PCR and primer extension methodology in a 3730 automated sequencer. All the polymorphisms analyzed in this report were in Hardly-Weingberg equilibrium.
rs10490924/ARMS2 and rs12603486/SERPINF1 each independently influenced (p<0.05) treatment response in functional and anatomical criteria while rs388862/CFHR1-3 showed influence (p<0.05) in anatomical and number of injection criteria. rs800292/CFH and rs7993418/VEGFR1 for anatomical criterion and rs1136287/SERPINF1, rs17611/C5 and smoking habit for number of injection criterion showed a significant association (p<0.05) with the treatment response.
ARMS2, CFH, CFHR1-3, SERPINF1, VEGFR1 and C5 risk or protective alleles and smoking habit affect the response to Ranibizumab in wet AMD. In addition, ARMS2, SERPINF1 and CFHR1-3 alleles have showed their response influence in more than one response evaluation criteria (Functional, anatomical or number of injection).
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