Study of interactions between HTRA1 gene polymorphism and retinal pigment epithelial phenotype in age-related macular degeneration

Abstract

Annotation. Age-related macular degeneration is a multifactorial nosology caused by the interaction of various risk factors, but the pathogenesis remains unclear. An alternative point of application in the pathogenesis of the disease was the product of the HTRA1 gene, which is actively expressed in retinal epithelial cells and modulates their response to stimuli. That is why the aim of our study was to elucidate the effect of the rs11200638 polymorphism of the HTRA1 gene on the occurrence and development of age-related macular degeneration and to determine the intensity of this pathological effect. The study group consisted of 291 individuals, while the comparison group consisted of 105 individuals of the appropriate age. Optical coherence tomography of the macular area of the retina using the ILM-RPE parameter was used to establish the diagnosis. Real-time polymerase chain reaction was used to detect polymorphism on the BioRad CFX 96 thermocycler-amplifier. Statistical processing of the results was performed by determining Hardy-Weinberg equilibrium, Kruskal-Wallace methods, logistic regression using OR and 95% CI curves and indicators of sensitivity and specificity. The study found a predominance of wild type among the comparison group, while heterozygous and mutant genotypes were almost equally distributed among patients with “dry” and “wet” forms of age-related macular degeneration (AMD). A statistically significant associative association was found between the mutant allele A and the occurrence of both atrophic (OR=7.75; 95% CI 3.87-15.49) and neovascular (OR=3.3; 95% CI 1, 89-5.91) forms of AMD (p<0.001). Subsequent analysis revealed a significant statistical relationship between variant AA and “wet” AMD (OR=21.3; 95% CI 2.57-176.8; p<0.001), as well as between heterozygous variant and “dry” (OR=7.7; 95% CI 3.8-15.46) and “wet” (OR=2.45; 95% CI 1.36-4.43) forms of the disease (p <0.01). In addition, the use of single nucleotide polymorphism (SNP) rs11200638 allows with a specificity of 59.2-98.4% and a sensitivity of 12.5-83.9% to diagnose AMD, depending on its form and the available genotype of the patient. Thus, our results indicate the high significance of the prognostic effect of the rs11200638 polymorphism of the HTRA1 gene on the development and progression of AMD, and the sensitivity and specificity indicators allow the use of the definition of this SNP to diagnose the disease.