The influence of the rs2010963 polymorphism of the VEGFA gene on the response to the treatment of the “wet” form of age-related macular degeneration

Abstract

Annotation. Age-related macular degeneration is one of the main causes of vision loss in the elderly. By 2040, the population with age-related macular degeneration (AMD) is expected to reach about 288 million. It was hypothesized that anti-VEGF therapy would significantly improve the vision and quality of life of patients with “wet” AMD. However, approximately one-third of patients do not benefit from this therapy, including due to macular fibrosis or retinal atrophy. It is believed that the role of genetic predisposition may also influence treatment resistance. Therefore, the aim of the study was to identify the response to treatment with aflibercept in patients with “wet” AMD with polymorphism variants rs2010963 of the VEGFA gene. The research group included 162 people who had a confirmed “wet” form of AMD, in contrast to which 105 people were included in the comparison group. The “wet” form of AMD was detected with the help of optical coherence tomography using the ILM-RPE parameter, while the patients received monthly intravitreal injections of the AVGF drug aflibercept (50 μl of solution – the recommended dose). Real-time polymerase chain reaction was used to determine the rs2010963 polymorphism of the VEGFA gene. Statistical processing of the obtained results was carried out using Statistica 10.0 and SPSS 23.0 programs. It was established that the presence of the mutant C allele increases the risk of resistance to anti-VEGF therapy both after the first injection and after the full course of treatment (p<0.05). A strong influence of the polymorphism after the therapy was observed in the areas of OCT 2, which corresponds to the inner upper part of the retina (OR=5.89; 95% CI 3.31 – 10.49) and OCT 3, which corresponds to the central area of ​​the retina (OR=4, 76; 95% CI 2.79 – 8.13). At the same time, there is an influence of mutant genotypes on treatment: yes, carrying both the heterozygous variant of ONP and the homozygous variant for the minor allele significantly contributed to the emergence of resistance to treatment (p<0.05). A pronounced degree of association of rs2010963 of the VEGFA gene with the emergence of resistance to the action of anti-VEGF drugs was revealed. Thus, the heterogeneity of RR and 95% CI indicators in different areas of the retina likely indicates a “zone-dependent” effect of rs2010963 of the VEGFA gene on the retina, which may be related to the peculiarities of its functioning and pathogenetic effect on the organ of vision.