Variability of the innate immunity genes TLR2, TLR3, TLR4, TLR6 among patients with simple primary and pseudoexfoliative clinical and pathogenetic forms of glaucoma, according to a multicenter study in the Russian Federation

In pseudoexfoliative syndrome (PES), extracellular material accumulates in the eye tissues, which can lead to the clinical features of primary open-angle glaucoma (POAG), with the development of pseudoexfoliative glaucoma (PEG). The genetic predisposition to the development of PES has been shown. Aim of the study was, in the simultaneous multicenter study, to conduct a clinical and genetic analysis of toll-like receptor genes TLR2, TLR3, TLR4, TLR6 polymorphism in groups of patients with simple primary glaucoma (SPG) and pseudoexfoliative glaucoma living in different geographical regions of the Russian Federation with an assessment of the possible prognostic significance of the identified differences. Material and methods . 648 patients with POAG were examined – 199 people with PEG and 350 with SPG from six S. Fyodorov Eye Microsurgery Federal State Institution branches (99 people were not described for this trait and were not included in the analysis when dividing patients into PEG/PP subgroups): Irkutsk – 50 people, Novosibirsk – 199 people, Cheboksary, Orenburg, Saint Petersburg, Khabarovsk – 100 people each. TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810) were genotyped using real time PCR with the Cyber Green (Litech, Russia) on a single instrument and reagent base in the Laboratory of Clinical Immunogenetics of Research Institute of Clinical and Experimental Lymphology – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS (Novosibirsk). Results and discussion. The deviation from the Hardy‒Weinberg distribution in the TLR4 299 was found among patients in Saint Petersburg, associated with a decrease in heterozygosity. For patients from Cheboksary, Saint Petersburg, Khabarovsk and Orenburg, in contrast to Novosibirsk, a significant (including after applying the Bonferroni correction) increase in the frequency (up to 100%) of the TLR2 753 ArgArg variant was found. For individual TLR complexes, the values of the odds ratio indicators for predicting the development of glaucoma with PES are significant, but they are offset by the Bonferroni correction. However, this may indicate the possible involvement of these constitutional factors of innate immunity in the formation of PES. Conclusions . The results of the study outline new directions in the development of approaches to the diagnosis and treatment of glaucoma.