Study of interactions between CFH gene polymorphism and retinal pigment epithelium phenotype in age-related macular degeneration
Authors: Malachkova N. V. , Mohammad Masa’deh Mohammad Mashhour 
Published: October 2022

Annotation. AMD (age-related macular degeneration) is one of the leading causes of blindness in the world, associated with the formation of extracellular deposits called drusen in the macula, i.e. in the central part of the retina. These drusen contain cellular debris and proteins, including components of the complement system, such as the regulator CFH (complement factor H). Complement dysregulation is believed to play a major role in the development of AMD. CFH acts through its ability to recognize polyanionic structures (eg, sulfated GAGs (glycosaminoglycans)) found in host tissues, and thus CFH inactivates any complement system (C3b) that is deposited. Importantly, the common CFH (Y402H) polymorphism was strongly associated with an increased risk of AMD. Recent studies have shown that the disease-associated allotype 402H interacts more poorly (compared to 402Y) with binding sites in the macula (eg, Bruch's membrane), where GAGs (glycosaminoglycans), heparan sulfate, and dermatan sulfate play a major role in mediating the interaction with CFH. Decreased binding of the 402H allotype may lead to complement dysregulation, leading to chronic local inflammation that may contribute to drusen accumulation and thus the initiation, development, and progression of AMD. That is why the goal of our study was to highlight the effect of the rs1061170 polymorphism of the CFH gene on the occurrence and development of age-related macular degeneration and to clarify the intensity of this pathological effect. The study group consisted of 291 people suffering from AMD (89 – with the “dry” form, 97 – with the “wet” form), the comparison group – 105 people without a history of ophthalmic pathology of the corresponding age. Optical coherence tomography (SOCT Copernicus “Optopol”) of the macular area of the retina was used in the study. We used the parameter ILM-RPE (internal limiting membrane-retinal pigmented epithelium). DNA was isolated from the biological material obtained by the buccal scraping method using the Bio-Rad Chelex ® 100 kit. Polymerase chain reaction was used to detect the rs1061170 polymorphism of the CFH gene. Statistical processing of the obtained results was carried out using Statistica 10 (StatSoft, Inc., USA) and SPSS 23.0 programs. The following were used: Hardy-Weinberg equilibrium (Hardy–Weinberg); Kruskal-Wallis test ANOVA by Ranks and Friedman ANOVA and Kendall Coeff. of Concordance; H-criterion; indicators of the odds ratio (OR; Odds Ratio – OR) and 95% probable interval (±95% CI; Confidence limit for means Interval – CI); used the method of analysis of operating characteristic curves (ROC – Receiver Operating Characteristic curve analysis); used special formulas using 2x2 tables. Our results confirm the high prognostic significance of the rs1061170 polymorphism of the CFH gene on the development and progression of AMD in the Ukrainian population. Indicators of specificity and sensitivity of SNP genotypes are ambiguous.