The Role Of HTRA Serine Peptidase 1, Vascular Endothelial Growth Factor А, Tumor Necrosis Factor Gene Polymorphisms in the Treatment Of Wet Age-Related Macular Degeneration

Abstract

Introduction. Age-related macular degeneration (AMD) of the retina is still considered the leading cause of vision loss in the elderly. The multifactoriality of the disease impairs the clinical effectiveness of modern AMD treatment methods. however, the study of single-nucleotide polymorphisms, in particular, of the HtrA serine peptidase 1 (HTRA1), vascular endothelial growth factor A (VEGF A) and tumor necrosis factor (TNF) genesis a promising link on the way to improve and develope more effective treatment strategies of the disease. The Aim of the Study. To investigate role of HTRA 1, VEGF A and TNF gene polymorphisms in the treatment of wet age-related macular degeneration. Materials and Methods. 162 people with diagnosed wet AMD took part in the investigation. They received anti-VEGF A therapy in the form of injections of aflibercept monthly for half a year. Structural changes of the eyes were studied using optical coherence tomography (OCT); polymerase chain reaction (PCR) studies were performed using a Bio-Rad CFX 96 apparatus (BioRad, USA) using a reagent package (Lytech, Russia). Statistical analysis of the obtained results was performed using a set of software packages Statistica 10 (StatSoft, Inc., USA) and SPSS 23.0. Results. It was revealed best prognostic significance in patients with the TC rs2010963 genotype of the VEGFA gene was registered during the analysis of OCT 2 (RR=2.7; 95% CI 1.556 – 4.8), OCT 4 (RR=2.9 ; 95% CI 1.7 – 5.03) and OCT 8 (RR=2.6; 95% CI 1.6 – 4.12) sections, while in patients with the CC genotype these indicators in the OCT 2 section were: RR= 6.1; 95% CI 3.66 – 10.27; in OCT zone 4 RR=4.9; 95% CI 2.9 – 8.29, and in the OCT section 8: RR=4.23; 95% CI 2.7 – 6.556, which indicates a more pronounced influence of the CC genotype. When analyzing rs1800629 of the TNF gene, the best prognostic significance of the GA genotype was established in the OCT 4 (RR=1.77; 95% CI 1.218 – 2.56) and OCT 8 (RR=1.9; 95% CI 1.17 – 3.175) areas (p-value less than 0.05), with the AA genotype in OCT 4 (RR=3.77; 95% CI 2.17 – 6.58), OCT 8 (RR=3.1; 95% CI 1 .7 – 5.59) zones and when evaluating changes in visual acuity of patients with wet AMD (RR=4.2; 95% CI 2 – 8.98). No statistically significant results were found in the evaluation of the HTRA1 gene rs11200638 (p-value more than 0.05). Conclusions. The data obtained in our study indicate a direct influence of the vascular endothelial growth factor A (rs2010963) and tumor necrosis factor (rs1800629) polymorphisms on the emergence of resistance to aflibercept. However, the study of this influence in the presence of the HtrA serine peptidase 1 gene rs11200638 requires further research.