Effect of Risk Alleles in CFH, C3, and VEGFA on the Response to Intravitreal Bevacizumab in Tunisian Patients with Neovascular Age-related Macular Degeneration

Abstract

Purpose. The aim of this pharmacogenetic study was to evaluate the impact of high-risk alleles in factor H, factor C3 and vascular endothelial growth factor (VEGF) on the response to intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD) in a Tunisian population.

Methods. Ninety patients with active neovascular AMD treated with intravitreal bevacizumab injections were enrolled in the study. Treatment response was evaluated by comparing BCVA at baseline and at 12 months. Patients were classified into either “poor responders” (PR) or “good responders” (GR). Single nucleotide polymorphism (SNP) genotyping was performed for rs1061170 in FH, rs2230199 in C3 andrs699947, rs2010963 and rs3025039 in VEGF. The association between genotype and visual response at 12 months was assessed.

Results. Seventy-seven participants were assigned to the GR group and 13 to the PR group. No correlation was found between FH, C3 and VEGF variant alleles and treatment response. However, haplotype analysis of rs699947 ((− 2578) C/A), rs2010963 ((+ 405) C/G) and rs3025039 ((+ 936) C/T) SNPs revealed that the AGT haplotype was associated with a poor response at 12months (p = 0.048). No association was found between treatment response and the cumulative effect of all high-risk alleles of C3, FH and VEGF. All three types of CNV were found in both groups at a comparable frequency.

Conclusions. The VEGF haplotype TGA could be used as a marker for poor visual prognosis in Tunisian patients with neovascular AMD treated with bevacizumab.

Zusammenfassung

Ziel. Das Ziel dieser pharmakogenetischen Studie war den Einfluss der risikoreichen Allelen Faktor H, Faktor C3 und VEGF in der Reaktion zu Intravitreal Bevacizumab bei Patienten mit neovaskulärer, altersbedingter Makuladegeneration (AMD) in der tunesischen Bevölkerung zu bewerten.

Methoden. Neunzig Patienten mit aktiver neovaskularer AMD welche mit Intravitreal Bevacizumab-Injektionen betreut worden sind, wurden in der Studie eingewickelt. Die Reaktion zur Behandlung wurde durch den Vergleich zwischen dem BCVA-Wert am Anfangspunkt und nach 12 Monaten bewertet. Die Patienten wurden entweder zu den „schlechten Reagierenden“ (PR) oder zu den „guten Reagierenden“ (GR) eingeordnet. Single nucleotide polymorphism (SNP) wurde zur Genotypisierung von rs1061170 in FH, von rs2230199 in C3, von andrs699947, rs2010963 und rs3025039 in VEGF durchgeführt. Die Vereinigung zwischen Genotyp und sichtbarer Reaktion nach 12 Monaten wurde beurteilt.

Resultate. Siebenundsiebzig Teilnehmer wurden zur GR Gruppe angeordnet und 13 zu der PR Gruppe. Es wurde keinen Unterschied bei FH, C3, und VEGF Allelenvarianten mit Behandlungsreaktionen festgestellt. Jedoch zeigte die Haplotyp Analyse von rs699947 ((− 2578) C/A), rs2010963 ((+ 405) C/G) und rs3025039 ((+ 936) C/T) SNPs dass das AGT Haplotyp nach 12 Monaten mit einer schlechten Reaktion verbunden ist (p = 0.048). Es wurde keine Verbindung zwischen der Behandlungsreaktion und der kumulativer Wirkung der risikoreichen Allelen C3, FH und VEGF festgestellt.

Ergebnisse. Der VEGF Halotyp TGA könnte als Marker für schlechte visuelle Prognosen bei tunesischen Patienten mit neovaskularer AMD, welche mit Bevacizumab behandelt werden, angewendet werden.

Key words

AMD - factor H - VEGF - C3 - anti-VEGF therapy

Schlüsselwörter

AMD - Faktor H - VEGF - C3 - anti-VEGF Therapie

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