A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma

Abstract

Aim — to study of gene polymorphisms affecting the effectiveness of timolol treatment of primary open-angle glaucoma.Patients and Methods. The study included 39 Russian patients (29 women and 10 men) aged 53 to 89 years old with a diagnosis of primary open-angle glaucoma (POAG). Intraocular pressure (IOP) was measured before the start of therapy and after 2 weeks during treatment. Сoefficient of decrease in IOP was calculated in percentage of its initial level (∆D). Patients were genotyped according to the polymorphic loci MMP1-160insG, MMP12A-82G, TIMP1C536T, ADRB1Arg389Gly, ADRB1Ser49Gly, NAT2Lys268Arg, GSTP1Ile105Val using the corresponding SNP-express reagent kits (NPF Lytech, Moscow).Results. No effect of MMP12A-82G, TIMP1C536T, ADRB1Arg389Gly, NAT2Lys268Arg polymorphisms on efficiency of reduction of IOP under action of thymolol in “best” eyes was revealed. The carriage of a homozygous genotype GSTP1Ile105Ile resulted in the best ophthalmic hypotensive effect of a timolol (∆D ≥ 20 %), which probability was 5.63 times higher in comparison with ∆D < 20 %. In the “worst” eyes, the association of carriage of a combination of wild genotypes GSTP1Ile105Ile×NAT2Lys268Lys with the best response of patients to timolol was revealed. The ophthalmic hypotensive effect of 10 ≤ ∆D < 20 % in such carriers was more than 11 times more likely than ∆D < 10 %.Conclusion. The carriage of the wild genotype GSTP1Ile105Ile determines the best ophthalmic hypotensive effect of timolol and can be a prognostic marker for the effective treatment of patients with POAG. The combination of wild genotypes GSTP1Ile105Ile×NAT2Lys268Lys can contribute to the better therapeutic effect of timolol, and mutant ones can prevent it.

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“…Official statistical data over the period in 2010-2018 on all the RF regions were taken from the open sources and applied as initial data in sociohygienic determinants and LEB levels. In conformity with the Methodical guidelines MR 2.1.10.0269-21 'Identification of sociohygienic determinants and prediction of a potential growth in life expectancy at birth for the RF population, regional differentiation taken into account' 11 , the list of the examined indicators included 148 socio-hygienic determinants that were conditionally aggregated into 6 groups: sanitary-epidemiological wellbeing (53 indicators), socio-demographic indicators (34), lifestyle-related indicators (30), economic indicators (14), public healthcare (9 indicators), nature and climate (8 indicators).…”

“…We selected polymorphic loci of candidate genes to analyze them in our study using the following criteria: 1) an association with knee OA established in European population by previous whole-genome studies (GWAS); 2) apparent functional significance of a polymorphism (regulatory potential, an association with expression and alternative gene splicing) [29,30]; 3) frequency of a polymorphism being not less than 5 %. Four SPNs of three genes were selected for the present study in accordance with these criteria.…”

“…We estimated functional effects produced by polymorphism of candidate genes that had significant associations with OA by using HaploReg (v4.1) 2 to examine regulatory potential [29,33] and GTExPortal 3 to examine influence exerted on gene expression and alternative splicing [30].…”

Molecular and genetic aspects of health risks and their association with adverse environmental conditions and diets (systemic review)

“…В источниках литературы приводятся данные об ассоциации генетических полиморфизмов Ile105Val и Ala114Val GSTP1 с офтальмопатологией у рабочих металлургического производства, контактирующих с химическим фактором и высокими температурами [29]. Показано, что GSTP1 Ile105Val может являться фактором риска как воспалительных, так и дистрофических изменений органа зрения [30].…”

Molecular and genetic aspects of health risks and their association with adverse environmental conditions and diets (systemic review)

“…Literature sources provide data on the association between GSTP1 Ile105Val and Ala114Val polymorphism and ophthalmic pathology in workers employed in metallurgy and exposed to chemical factors and high temperatures [29]. The GSTP1 Ile105Val genotype was shown to be a potential risk factor causing both inflammatory and dystrophic changes in the eye [30].…”