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

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...

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Main Authors: A. L. Onishchenko, N. V. Maltseva, A. Sh. Smirnova, O. M. Kazantseva, S. I. Makogon
Format: Article
Language:Russian
Published: Ophthalmology Publishing Group 2021-10-01
Series:Oftalʹmologiâ
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Online Access:https://www.ophthalmojournal.com/opht/article/view/1612
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author A. L. Onishchenko
N. V. Maltseva
A. Sh. Smirnova
O. M. Kazantseva
S. I. Makogon
author_facet A. L. Onishchenko
N. V. Maltseva
A. Sh. Smirnova
O. M. Kazantseva
S. I. Makogon
author_sort A. L. Onishchenko
collection DOAJ
description 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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spelling doaj-art-bc6b3f1a053547fbae6399b33290cd7c2025-08-20T04:00:20ZrusOphthalmology Publishing GroupOftalʹmologiâ1816-50952500-08452021-10-0118354655110.18008/1816-5095-2021-3-546-551792A Personalized Approach to the Treatment of Primary Open-Angle GlaucomaA. L. Onishchenko0N. V. Maltseva1A. Sh. Smirnova2O. M. Kazantseva3S. I. Makogon4Novokuznetsk State Institute of Postgraduate MedicineNovokuznetsk State Institute of Postgraduate MedicineNovokuznetsk State Institute of Postgraduate MedicineNovokuznetsk State Institute of Postgraduate MedicineNovokuznetsk State Institute of Postgraduate MedicineAim — 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.https://www.ophthalmojournal.com/opht/article/view/1612glaucomatimololgenepolymorphismn-acetyltransferase 2glutathione-s-transferase p1ophthalmic hypotensive effect
spellingShingle A. L. Onishchenko
N. V. Maltseva
A. Sh. Smirnova
O. M. Kazantseva
S. I. Makogon
A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma
Oftalʹmologiâ
glaucoma
timolol
gene
polymorphism
n-acetyltransferase 2
glutathione-s-transferase p1
ophthalmic hypotensive effect
title A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma
title_full A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma
title_fullStr A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma
title_full_unstemmed A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma
title_short A Personalized Approach to the Treatment of Primary Open-Angle Glaucoma
title_sort personalized approach to the treatment of primary open angle glaucoma
topic glaucoma
timolol
gene
polymorphism
n-acetyltransferase 2
glutathione-s-transferase p1
ophthalmic hypotensive effect
url https://www.ophthalmojournal.com/opht/article/view/1612
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