phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"10.37489/2588-0527-2020-1-26-34phgenomics-186Research ArticleПЕРСОНАЛИЗИРОВАННАЯ ТЕРАПИЯPERSONALIZED THERAPYПрикладная фармакогенетика для персонализации ведения пациентов с глаукомойPractical pharmacogenetics for personalized management of glaucoma patientshttps://orcid.org/0000-0001-5081-414XМошетоваЛ. К.MoshetovaL. K.

Мошетова Лариса Константиновна - д. м. н., профессор, академик РАН, зав. кафедрой офтальмологии, президент

SPIN-код: 5697-6825

Москва

Moshetova Larisa K. - MD, Professor, Academician of the Russian Academy of Sciences, Head of the Department of Ophthalmology, President

SPIN code: 5697-6825

Moscow

https://orcid.org/0000-0001-7886-7702СошинаМ. М.SoshinaM. M.

Сошина Мария Михайловна - аспирант кафедры офтальмологии

SPIN-код: 3177-3060

Москва

Soshina Maria M. - PhD student of the Department of ophthalmology 

SPIN code: 3177-3060

Moscow

greenmaha@yadex.ruhttps://orcid.org/0000-0002-4989-7467ТуркинаК. И.TurkinaK. I.

Туркина Ксения Ивановна - к. м. н., доцент кафедры офтальмологии

SPIN-код: 3187-4280

Москва

Turkina Ksenia I. - Сandidate of medical Sciences, docent of the Department of ophthalmology 

SPIN code: 3187-4280

Moscow

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияRussian Medical Academy of Continuing Professional Education of the Ministry of Health of RussiaRussian Federation202028122020012634Copyright © Мошетова Л.К., Сошина М.М., Туркина К.И., 20202020Мошетова Л.К., Сошина М.М., Туркина К.И.Moshetova L.K., Soshina M.M., Turkina K.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/186

В настоящее время, с учётом широкого применения достижений фармакогенетики во всех отраслях медицины, стало возможным проведения таких исследований и в офтальмологии. В настоящий момент, уже были проведены исследования самых часто применяемых препаратов для лечения глаукомы. Были найдены закономерности между генотипами пациентов и частотой возникновения нежелательных лекарственных реакций. Изучение фармакогенетики антиглаукомных препаратов и внедрение фармакогенетического тестирования позволит офтальмологам подобрать рациональное, безопасное и эффективное лечение в короткие сроки, что позволит существенно улучшить качество оказываемой помощи.

At present, taking into account the widespread application of pharmacogenetics’ achievements to all branches of medicine, it has become possible to conduct such research in ophthalmology. At the moment, the studies on the most broadly used glaucoma medications have been carried out. The correlations between patients’ genotypes and the frequency of occurrence of adverse side effects have been found. The further exploration of the pharmacogenetics of the glaucoma medications and the introduction of pharmacogenetic testing will enable ophthalmologists to assign a rational, safe, and effective treatment in the short time, which will considerably improve the quality of provided aid.

глаукомафармакогенетикатимололлатанопростCYP2D6бринзоламидбримонидинglaucomapharmacogeneticstimolollatanoprostCYP2D6brinzolamidebrimonidineReferencesНациональное руководство по глаукоме: для практикующих врачей / под ред. Е.А. Егорова, Ю.С. Астахова, В.П. Еричева. – 3-е изд. – М.: ГЭОТАР-Медиа; 2015. – 456 с. [Natsional’noe rukovodstvo po glaukome dlya praktikuyushchikh vrachei, 3-e izdanie. Pod red. EA Egorova, YuS Astakhova, VP Ericheva. Moscow: GEOTAR-Media; 2015. (In Russ).].Национальное руководство по глаукоме: для практикующих врачей / под ред. Е.А. Егорова, Ю.С. Астахова, В.П. Еричева. – 3-е изд. – М.: ГЭОТАР-Медиа; 2015. – 456 с. [Natsional’noe rukovodstvo po glaukome dlya praktikuyushchikh vrachei, 3-e izdanie. Pod red. EA Egorova, YuS Astakhova, VP Ericheva. Moscow: GEOTAR-Media; 2015. (In Russ).].Мошетова Л.К., Сошина М.М., Сычев Д.А., Туркина К.И. Фармакогенетика тимолола // Вестник офтальмологии. 2019;135(3):137-143. [Moshetova LK, Soshina MM, Sychev DA, Turkina KI. Pharmacogenetics of timolol. Vestnik oftal`mologii. 2019;135(3):137–143 (In Russ).]. DOI: 10.17116/oftalma2019135031137.Мошетова Л.К., Сошина М.М., Сычев Д.А., Туркина К.И. Фармакогенетика тимолола // Вестник офтальмологии. 2019;135(3):137-143. [Moshetova LK, Soshina MM, Sychev DA, Turkina KI. Pharmacogenetics of timolol. Vestnik oftal`mologii. 2019;135(3):137–143 (In Russ).]. DOI: 10.17116/oftalma2019135031137.Куроедов А.В., Брежнев А.Ю. Продолжительность гипотензивного действия антиглаукомных препаратов // РМЖ. Клиническая офтальмология. 2016;(4):214–219. [Kuroyedov AV, Brezhnev AYu. The duration of the hypotensive action of anti-glaucoma medicines. RMJ. Klinicheskaya oftal’mologiya. 2016;(4):214–219. (In Russ).]. DOI: 10.21689/2311-7729-2016-16-4-214-219.Куроедов А.В., Брежнев А.Ю. Продолжительность гипотензивного действия антиглаукомных препаратов // РМЖ. Клиническая офтальмология. 2016;(4):214–219. [Kuroyedov AV, Brezhnev AYu. The duration of the hypotensive action of anti-glaucoma medicines. RMJ. Klinicheskaya oftal’mologiya. 2016;(4):214–219. (In Russ).]. DOI: 10.21689/2311-7729-2016-16-4-214-219.Нестеров А.П. Глаукома. – М.: Медицина; 1995. – 256 с. [Nesterov AP. Glaukoma. Moscow: Meditsina; 1995. (In Russ).].Нестеров А.П. Глаукома. – М.: Медицина; 1995. – 256 с. [Nesterov AP. Glaukoma. Moscow: Meditsina; 1995. (In Russ).].Мошетова Л.К., Сошина М.М., Сычев Д.А., Туркина К.И. и др. Полипрагмазия в офтальмологической практике // Врач. 2018;29(7):40–43. [Moshetova LK, Soshina MM, Sychev DA, Turkina KI et al. Polipragmaziya v oftal’mologicheskoj praktike. Vrach. 2018;29(7):40-43. (In Russ).]. DOI: 10.29296/25877305-2018-07-08.Мошетова Л.К., Сошина М.М., Сычев Д.А., Туркина К.И. и др. Полипрагмазия в офтальмологической практике // Врач. 2018;29(7):40–43. [Moshetova LK, Soshina MM, Sychev DA, Turkina KI et al. Polipragmaziya v oftal’mologicheskoj praktike. Vrach. 2018;29(7):40-43. (In Russ).]. DOI: 10.29296/25877305-2018-07-08.Офтальмология: национальное руководство / под ред. Аветисова С.Э., Егорова Е.А., Мошетовой Л.К., Нероева В.В., Тахчиди Х.П. – М.: ГЭОТАР-Медиа; 2013:767–769. [Oftal’mologiya: natsional’noe rukovodstvo. Pod red. Avetisova SE, Egorova EA, Moshetovoi LK, Neroeva VV, Takhchidi KhP. Moscow: GEOTAR-Media; 2013:767–769. (In Russ).].Офтальмология: национальное руководство / под ред. Аветисова С.Э., Егорова Е.А., Мошетовой Л.К., Нероева В.В., Тахчиди Х.П. – М.: ГЭОТАР-Медиа; 2013:767–769. [Oftal’mologiya: natsional’noe rukovodstvo. Pod red. Avetisova SE, Egorova EA, Moshetovoi LK, Neroeva VV, Takhchidi KhP. Moscow: GEOTAR-Media; 2013:767–769. (In Russ).].Nouri-Mahdavi K, Hoffman D, Coleman AL, Liu G, Li G, Gaasterland D., Caprioli J. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111(9):1627– 1635. DOI: 10.1016/j.ophtha.2004.02.017.Nouri-Mahdavi K, Hoffman D, Coleman AL, Liu G, Li G, Gaasterland D., Caprioli J. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111(9):1627– 1635. DOI: 10.1016/j.ophtha.2004.02.017.Куроедов А.В. Перспективы применения комбинированных антиглаукомных препаратов (обзор литературы) // Клиническая офтальмология. 2007;(4):176–180. [Kuroyedov AV. Prospects of combined antiglaucoma drugs usage (literary review). Klinicheskaya oftal’mologiya. 2007;(4):176–180. (In Russ).].Куроедов А.В. Перспективы применения комбинированных антиглаукомных препаратов (обзор литературы) // Клиническая офтальмология. 2007;(4):176–180. [Kuroyedov AV. Prospects of combined antiglaucoma drugs usage (literary review). Klinicheskaya oftal’mologiya. 2007;(4):176–180. (In Russ).].Ghate D, Edelhauser HF. Barriers to glaucoma drug delivery. Journal of Glaucoma. 2008;17(2):147–156. DOI: 10.1097/ijg.0b013e31814b990d.Ghate D, Edelhauser HF. Barriers to glaucoma drug delivery. Journal of Glaucoma. 2008;17(2):147–156. DOI: 10.1097/ijg.0b013e31814b990d.Juha-Matti Korte, Timo K, Matti K Saari. Systemic bioavailability and cardiopulmonary effects of 0.5% timolol eyedrops. Graefes Arch Clin Exp Ophthalmol. 2002 Jun;240(6):430-435. DOI: 10.1007/s00417-002-0462-2.Juha-Matti Korte, Timo K, Matti K Saari. Systemic bioavailability and cardiopulmonary effects of 0.5% timolol eyedrops. Graefes Arch Clin Exp Ophthalmol. 2002 Jun;240(6):430-435. DOI: 10.1007/s00417-002-0462-2.Zimmerman TJ, Kaufman HE. Timolol, a beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol. 1977 Apr;95(4):601– 464. DOI: 10.1001/archopht.1977.04450040067008.Zimmerman TJ, Kaufman HE. Timolol, a beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol. 1977 Apr;95(4):601– 464. DOI: 10.1001/archopht.1977.04450040067008.Егоров Е.А. Нежелательные явления гипотензивной терапии глаукомы // РМЖ. Клиническая офтальмология. 2007;8(4):144–147. [Egorov EA. Undesirable effects of hypotensive treatment. RMJ. Klinicheskaya oftal’mologiya. 2007;8(4):144-147. (In Russ).].Егоров Е.А. Нежелательные явления гипотензивной терапии глаукомы // РМЖ. Клиническая офтальмология. 2007;8(4):144–147. [Egorov EA. Undesirable effects of hypotensive treatment. RMJ. Klinicheskaya oftal’mologiya. 2007;8(4):144-147. (In Russ).].Nieminen T, Lehtimäki T, Mäenpää J et al. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest. 2007;67(2):237–245. DOI: 10.1080/00365510601034736Nieminen T, Lehtimäki T, Mäenpää J et al. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest. 2007;67(2):237–245. DOI: 10.1080/00365510601034736Higginbotham EJ, Lee DA. Clinical Guide to Glaucoma management. Butterwort & Heinemann Elsevier Inc; 2004:107–122.Higginbotham EJ, Lee DA. Clinical Guide to Glaucoma management. Butterwort & Heinemann Elsevier Inc; 2004:107–122.Yarangümeli A, Kural G. Are there any benefits of Betoptic S (betaxolol HCl ophthalmic suspension) over other β-blockers in the treatment of glaucoma? Expert Opin Pharmacother. 2004:5(5);1071–1081. DOI: 10.1517/14656566.5.5.1071.Yarangümeli A, Kural G. Are there any benefits of Betoptic S (betaxolol HCl ophthalmic suspension) over other β-blockers in the treatment of glaucoma? Expert Opin Pharmacother. 2004:5(5);1071–1081. DOI: 10.1517/14656566.5.5.1071.Егоров Е.А. и др. Офтальмофармакология. – М.: «Геотар–Мед»; 2004. – 202 с. [Egorov EA et al. Oftal’mofarmakologiya. Moscow: «Geotar– Med»; 2004. (In Russ).].Егоров Е.А. и др. Офтальмофармакология. – М.: «Геотар–Мед»; 2004. – 202 с. [Egorov EA et al. Oftal’mofarmakologiya. Moscow: «Geotar– Med»; 2004. (In Russ).].Volotinen M, Turpeinen M, Tolonen A et al. Timolol metabolism in human liver microsomes is mediated principally by CYP2D6. Drug Metab Dispos. 2007;35(7):1135–1141. DOI: 10.1124/dmd.106.012906.Volotinen M, Turpeinen M, Tolonen A et al. Timolol metabolism in human liver microsomes is mediated principally by CYP2D6. Drug Metab Dispos. 2007;35(7):1135–1141. DOI: 10.1124/dmd.106.012906.Zhang T, Xiang CD, Gale D et al. Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos. 2008;36(7):1300–1307. DOI: 10.1124/dmd.108.021121.Zhang T, Xiang CD, Gale D et al. Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos. 2008;36(7):1300–1307. DOI: 10.1124/dmd.108.021121.Volotinen M, Hakkola J, Pelkonen O et al. Metabolism of ophthalmic timolol: new aspects of an old drug. Basic Clin Pharmacol Toxicol. 2011;108(5):297–303. DOI: 10.1111/j.1742-7843.2011.00694.x.Volotinen M, Hakkola J, Pelkonen O et al. Metabolism of ophthalmic timolol: new aspects of an old drug. Basic Clin Pharmacol Toxicol. 2011;108(5):297–303. DOI: 10.1111/j.1742-7843.2011.00694.x.Fourtillan JB, Courtois P, Lefebvre MA, Girault J. Pharmacokinetics of oral timolol studied by mass fragmentography. Eur J Clin Pharmacol. 1981;19(3):193–196. DOI: 10.1007/bf00561948Fourtillan JB, Courtois P, Lefebvre MA, Girault J. Pharmacokinetics of oral timolol studied by mass fragmentography. Eur J Clin Pharmacol. 1981;19(3):193–196. DOI: 10.1007/bf00561948Кукес В.Г., Грачев С.В., Сычев Д.А., Раменская Г.В. Метаболизм лекарственных средств: научные основы персонализированной медицины. – М.: ГЭОТАР-Медиа; 2008. [Kukes VG, Grachev SV, Sychev DA, Ramenskaya GV. Metabolizm lekarstvennykh sredstv: nauchnye osnovy personalizirovannoi meditsiny. Moscow: GEOTAR-Media; 2008. (In Russ).].Кукес В.Г., Грачев С.В., Сычев Д.А., Раменская Г.В. Метаболизм лекарственных средств: научные основы персонализированной медицины. – М.: ГЭОТАР-Медиа; 2008. [Kukes VG, Grachev SV, Sychev DA, Ramenskaya GV. Metabolizm lekarstvennykh sredstv: nauchnye osnovy personalizirovannoi meditsiny. Moscow: GEOTAR-Media; 2008. (In Russ).].Кукес В.Г., Сычёв Д.А. Клиническая фармакология. – М.: ГЭОТАР-Медиа; 2015 [Kukes VG, Sychev DA. Klinicheskaya farmakologiya. Moscow: GEOTAR-Media; 2015. (In Russ).].Кукес В.Г., Сычёв Д.А. Клиническая фармакология. – М.: ГЭОТАР-Медиа; 2015 [Kukes VG, Sychev DA. Klinicheskaya farmakologiya. Moscow: GEOTAR-Media; 2015. (In Russ).].Sheldon HP et al. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine. J Clin Psychiatry. 2013;74(6):614–621. DOI: 10.4088/jcp.12m07807.Sheldon HP et al. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine. J Clin Psychiatry. 2013;74(6):614–621. DOI: 10.4088/jcp.12m07807.Абдрашитов Р.Х., Гильдеева Г.Н., Раменская Г.В., Смирнов В.В. Обзор существующих методик оценки активности CYP2D6 с применением экзогенных и эндогенных маркеров // Фармакокинетика и фармакодинамика. 2015;(1):4–11. [Abdrashitov AD, Gildeeva GN, Ramenskaya GV, Smirnov VV. Review of existing methodologies to assess the activity of CYP2D6 using exogenous and endogenous markers. Farmakokinetika i farmakodinamika. 2015;(1):4–11. (In Russ).].Абдрашитов Р.Х., Гильдеева Г.Н., Раменская Г.В., Смирнов В.В. Обзор существующих методик оценки активности CYP2D6 с применением экзогенных и эндогенных маркеров // Фармакокинетика и фармакодинамика. 2015;(1):4–11. [Abdrashitov AD, Gildeeva GN, Ramenskaya GV, Smirnov VV. Review of existing methodologies to assess the activity of CYP2D6 using exogenous and endogenous markers. Farmakokinetika i farmakodinamika. 2015;(1):4–11. (In Russ).].Сычев Д.А. Фармакогенетическое тестирование: клиническая интерпритация результатов. Рекомендации для практикующих врачей. – М.: Литех; 2011:27–30. [Sychev DA. Farmakogeneticheskoe testirovanie: klinicheskaya interpritaciya rezul’tatov. Rekomendacii dlya praktikuyushchih vrachej. Moscow: Litekh; 2011:27–30. (In Russ).].Сычев Д.А. Фармакогенетическое тестирование: клиническая интерпритация результатов. Рекомендации для практикующих врачей. – М.: Литех; 2011:27–30. [Sychev DA. Farmakogeneticheskoe testirovanie: klinicheskaya interpritaciya rezul’tatov. Rekomendacii dlya praktikuyushchih vrachej. Moscow: Litekh; 2011:27–30. (In Russ).].Yang Y, Wu K, Yuan H, Yu M. Cytochrome oxidase 2D6 gene polymorphism in primary open-angle glaucoma with various effects to ophthalmic timolol. J Ocul Pharmacol Ther. 2009;25(2):163–171. DOI: 10.1089/jop.2008.0028.Yang Y, Wu K, Yuan H, Yu M. Cytochrome oxidase 2D6 gene polymorphism in primary open-angle glaucoma with various effects to ophthalmic timolol. J Ocul Pharmacol Ther. 2009;25(2):163–171. DOI: 10.1089/jop.2008.0028.Сычев Д.А., Рожков А.В., Алексеев И.Б. Фармакогенетика при лечении глаукомы: настоящее и будущее // Фармакогенетика и Фармакогеномика. 2016;(2):13–17. Sychev DA, Rozkov AV, Alekseev IB. Pharmacogenetics for glaucoma:present and future. Farmakogenetika i Farmakogenomika. 2016;(2):13–17. (In Russ).].Сычев Д.А., Рожков А.В., Алексеев И.Б. Фармакогенетика при лечении глаукомы: настоящее и будущее // Фармакогенетика и Фармакогеномика. 2016;(2):13–17. Sychev DA, Rozkov AV, Alekseev IB. Pharmacogenetics for glaucoma:present and future. Farmakogenetika i Farmakogenomika. 2016;(2):13–17. (In Russ).].Yuan H, Yu M, Yang Y et al. Association of CYP2D6 Single-Nucleotide Polymorphism with Response to Ophthalmic Timolol in Primary Open-Angle Glaucoma-a pilot study. J Ocul Pharmacol Ther. 2010;26(5):497–501. DOI: 10.1089/jop.2010.0013.Yuan H, Yu M, Yang Y et al. Association of CYP2D6 Single-Nucleotide Polymorphism with Response to Ophthalmic Timolol in Primary Open-Angle Glaucoma-a pilot study. J Ocul Pharmacol Ther. 2010;26(5):497–501. DOI: 10.1089/jop.2010.0013.Nieminem T, Uusitalo H, Maenpaa J et al. Polymorphisms of genes CYP2D6, ADRB1, and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. Eur J Clin Pharmacol. 2005;61(11):811–819. DOI: 10.1007/s00228-005-0052-4.Nieminem T, Uusitalo H, Maenpaa J et al. Polymorphisms of genes CYP2D6, ADRB1, and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. Eur J Clin Pharmacol. 2005;61(11):811–819. DOI: 10.1007/s00228-005-0052-4.Brayfield A. (ed.) Timolol Maleate. Martindale: Complete Drug Reference. London: Pharmaceutical Press. 2016. [cited 2017 May 11]. Available from: https://clck.ru/SFmcHBrayfield A. (ed.) Timolol Maleate. Martindale: Complete Drug Reference. London: Pharmaceutical Press. 2016. [cited 2017 May 11]. Available from: https://clck.ru/SFmcHBrauner SC, Chen TC, Hutchinson BT et al. The course of glaucoma during pregnancy: a retrospective case series. Arch Ophthalmol. 2006;124(8):1089–1094. DOI: 10.1001/archopht.124.8.1089.Brauner SC, Chen TC, Hutchinson BT et al. The course of glaucoma during pregnancy: a retrospective case series. Arch Ophthalmol. 2006;124(8):1089–1094. DOI: 10.1001/archopht.124.8.1089.Mendez-Hernandez C, Garcia-Feijoo J, Saenz-Frances F et al. Topical intraocular pressure therapy effects on pregnancy. Clin Ophthalmol. 2012;6:1629–1632. DOI: 10.2147/opth.s36712.Mendez-Hernandez C, Garcia-Feijoo J, Saenz-Frances F et al. Topical intraocular pressure therapy effects on pregnancy. Clin Ophthalmol. 2012;6:1629–1632. DOI: 10.2147/opth.s36712.Wagenvoort AM, van Vugt JM, Sobotka M, van Geijn HP. Topical timolol therapy in pregnancy: is it safe for the fetus? Teratology. 1998;58:258–262. DOI: 10.1002/(sici)10969926(199812)58:6%3C258::aidtera7% 3E3.0.co;2-b.Wagenvoort AM, van Vugt JM, Sobotka M, van Geijn HP. Topical timolol therapy in pregnancy: is it safe for the fetus? Teratology. 1998;58:258–262. DOI: 10.1002/(sici)10969926(199812)58:6%3C258::aidtera7% 3E3.0.co;2-b.Gaikovitch EA, Cascorbi I, Mrozikiewicz PM, et al. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol. 2003;59(4):303–312. DOI: 10.1007/s00228-003-0606-2.Gaikovitch EA, Cascorbi I, Mrozikiewicz PM, et al. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol. 2003;59(4):303–312. DOI: 10.1007/s00228-003-0606-2.Леванов А.Н., Игнатьев И.В., Сычев Д.А. и др. Связь генетического полиморфизма бета-адренорецепторов с эффективностью терапии бета-адреноблокаторами у больных сердечно-сосудистой патологией // Саратовский научно-медицинский журнал. 2009;1(5):41–44. [Levanov AN, Ignatyev IV, Sychev DA et al. Beta-adrenoreceptors genetic polymorphism connection with beta-bloker therapy efficacy in patients with cardiovascular disorders. Saratov Journal of Medical Scientific Research. 2009;1(5):41–44. (In Russ).].Леванов А.Н., Игнатьев И.В., Сычев Д.А. и др. Связь генетического полиморфизма бета-адренорецепторов с эффективностью терапии бета-адреноблокаторами у больных сердечно-сосудистой патологией // Саратовский научно-медицинский журнал. 2009;1(5):41–44. [Levanov AN, Ignatyev IV, Sychev DA et al. Beta-adrenoreceptors genetic polymorphism connection with beta-bloker therapy efficacy in patients with cardiovascular disorders. Saratov Journal of Medical Scientific Research. 2009;1(5):41–44. (In Russ).].Pacanowski AM, Johnson JA. PharmGKB submission update: IX. ADRB1 gene summary. Pharmacol Rev. 2007;59(1):2–4. DOI: 10.1124/pr.59.1.6.Pacanowski AM, Johnson JA. PharmGKB submission update: IX. ADRB1 gene summary. Pharmacol Rev. 2007;59(1):2–4. DOI: 10.1124/pr.59.1.6.Levin MC, Marullo S, Muntaner O et al. The myocardium — protective Gly49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desentization and down — regulation. J Biol Chem 2002;277(34):30429–30435. DOI: 10.1074/jbc.m200681200.Levin MC, Marullo S, Muntaner O et al. The myocardium — protective Gly49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desentization and down — regulation. J Biol Chem 2002;277(34):30429–30435. DOI: 10.1074/jbc.m200681200.Moore JD, Mason DA, Green SA et al. Racial differences in the frequencies of cardiac beta 1-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C. Hum Mutat. 1999;14(3):271. DOI: 10.1002/(sici)1098-1004(1999)14:3%3C271::aid-humu14%3E3.0.co;2-q.Moore JD, Mason DA, Green SA et al. Racial differences in the frequencies of cardiac beta 1-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C. Hum Mutat. 1999;14(3):271. DOI: 10.1002/(sici)1098-1004(1999)14:3%3C271::aid-humu14%3E3.0.co;2-q.Muszkat M, Stein CM. Pharmacogenetics and response to betaadrenergic receptor antagonists in heart failure. Clin Pharmacol Ther. 2005;77(3):123–126. DOI: 10.1016/j.clpt.2004.10.007.Muszkat M, Stein CM. Pharmacogenetics and response to betaadrenergic receptor antagonists in heart failure. Clin Pharmacol Ther. 2005;77(3):123–126. DOI: 10.1016/j.clpt.2004.10.007.Johnson JA, Zinch I, Puckett BJ, et al. Beta1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003;74(1):44–52. DOI: 10.1016/s0009-9236(03)00068-7.Johnson JA, Zinch I, Puckett BJ, et al. Beta1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003;74(1):44–52. DOI: 10.1016/s0009-9236(03)00068-7.Sandberg A, Blomqvist I, Jonsson UE et al. Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets. Eur J Clin Pharmacol. 1988;33. Suppl:S9-14. DOI: 10.1007/bf00578406.Sandberg A, Blomqvist I, Jonsson UE et al. Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets. Eur J Clin Pharmacol. 1988;33. Suppl:S9-14. DOI: 10.1007/bf00578406.Sofowora GG, Dishy V, Muszkat M et al. A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to betablockade. Clin Pharmacol Ther. 2003;73(4):366–371. DOI: 10.1016/s0009-9236(02)17734-4.Sofowora GG, Dishy V, Muszkat M et al. A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to betablockade. Clin Pharmacol Ther. 2003;73(4):366–371. DOI: 10.1016/s0009-9236(02)17734-4.Inagaki Y, Mashima Y, Fuse N et al. Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma. Mol Vis. 2006; 12:673–680.Inagaki Y, Mashima Y, Fuse N et al. Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma. Mol Vis. 2006; 12:673–680.Schwartz SG, Puckett BJ, Allen RC et al. Beta1-adrenergic receptor polymorphisms and clinical efficacy of betaxolol hydrochloride in normal volunteers. Ophthalmology. 2005; 112(12):2131–2136. DOI: 10.1016/j.ophtha.2005.08.014.Schwartz SG, Puckett BJ, Allen RC et al. Beta1-adrenergic receptor polymorphisms and clinical efficacy of betaxolol hydrochloride in normal volunteers. Ophthalmology. 2005; 112(12):2131–2136. DOI: 10.1016/j.ophtha.2005.08.014.Liggett SB. Pharmacogenomics of beta-1 and beta-2 adrenergic receptors. Pharmacology. 2000;61:167-73. DOI: 10.1159/000028397Liggett SB. Pharmacogenomics of beta-1 and beta-2 adrenergic receptors. Pharmacology. 2000;61:167-73. DOI: 10.1159/000028397Parola AL, Kobilka BK. The peptide product of a 5` leader cistron in the beta 2 adrenergic receptor mRNA inhibits receptor synthesis. J BiolChem. 1994;269(6):4497–4505.Parola AL, Kobilka BK. The peptide product of a 5` leader cistron in the beta 2 adrenergic receptor mRNA inhibits receptor synthesis. J BiolChem. 1994;269(6):4497–4505.Green SA, Cole G, Jacinto M et al. A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem. 1993;268(31):23116-21.Green SA, Cole G, Jacinto M et al. A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem. 1993;268(31):23116-21.McCarty CA, Burmester JK, Mukesh BN et al. Intraocular pressure response to topical beta-blockers associated with an ADRB2 single-nucleotide polymorphism. Arch Ophthalmol. 2008;126(7):959-63. DOI: 10.1001/archopht.126.7.959.McCarty CA, Burmester JK, Mukesh BN et al. Intraocular pressure response to topical beta-blockers associated with an ADRB2 single-nucleotide polymorphism. Arch Ophthalmol. 2008;126(7):959-63. DOI: 10.1001/archopht.126.7.959.Fuchsjager-Maryl G, Markovic O, Losert D et al. Polymorphism of the beta-2 adrenoreceptor and IOP lowering potency of topical timolol in healthy subjects. Mol Vis. 2005;23:811-815.Fuchsjager-Maryl G, Markovic O, Losert D et al. Polymorphism of the beta-2 adrenoreceptor and IOP lowering potency of topical timolol in healthy subjects. Mol Vis. 2005;23:811-815.McLaren N, Reed DM, Musch DC et al. Evaluation of the beta2- adrenergic receptor gene as a candidate glaucoma gene in 2 ancestral populations. Arch Ophthalmol. 2007;125(1):105–111. DOI: 10.1001/archopht.125.1.105McLaren N, Reed DM, Musch DC et al. Evaluation of the beta2- adrenergic receptor gene as a candidate glaucoma gene in 2 ancestral populations. Arch Ophthalmol. 2007;125(1):105–111. DOI: 10.1001/archopht.125.1.105Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels. Available from: https://clck.ru/SFnBbTable of Valid Genomic Biomarkers in the Context of Approved Drug Labels. Available from: https://clck.ru/SFnBbАстахов Ю.С., Нечипоренко П.А. Аналоги простагландинов: прошлое, настоящее, будущее // Офтальмологические ведомости. – 2017. – Т. 10. – № 1. – С. 40–52. [Astakhov YuS, Nechiporenko PA. Prostaglandin analogues: past, present, and future. Ophtalmology Journal. 2017;10(1):40–52. (In Russ).]. DOI: 10.17816/OV10140-52Астахов Ю.С., Нечипоренко П.А. Аналоги простагландинов: прошлое, настоящее, будущее // Офтальмологические ведомости. – 2017. – Т. 10. – № 1. – С. 40–52. [Astakhov YuS, Nechiporenko PA. Prostaglandin analogues: past, present, and future. Ophtalmology Journal. 2017;10(1):40–52. (In Russ).]. DOI: 10.17816/OV10140-52Stjernschantz J, Resul B. Phenyl substituted prostaglandin analogs for glaucoma treatment. Drugs Future. 1992;17(8):691–704. DOI: 10.1358/dof.1992.017.08.187766.Stjernschantz J, Resul B. Phenyl substituted prostaglandin analogs for glaucoma treatment. Drugs Future. 1992;17(8):691–704. DOI: 10.1358/dof.1992.017.08.187766.Stjernschantz J, Alm A. Latanoprost as a new horizon in the medical management of glaucoma. Curr Opin Ophthalmol. 1996;7(2):11–17. DOI: 10.1097/00055735-199604000-00003.Stjernschantz J, Alm A. Latanoprost as a new horizon in the medical management of glaucoma. Curr Opin Ophthalmol. 1996;7(2):11–17. DOI: 10.1097/00055735-199604000-00003.Walters TR, DuBiner HB, Carpenter SP et al. 24-Hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, randomized, comparative clinical trial. Surv Ophthalmol. 2004;49 Suppl 1:S26–35. DOI: 10.1016/j.sur-vophthal.2003.12.017.Walters TR, DuBiner HB, Carpenter SP et al. 24-Hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, randomized, comparative clinical trial. Surv Ophthalmol. 2004;49 Suppl 1:S26–35. DOI: 10.1016/j.sur-vophthal.2003.12.017.Bill A. Conventional and uveoscleral drainage of aqueous humour in the cynomolgus monkey (Macaca irus) at normal and high intraocular pressures. Exp Eye Res. 1966;5:45–54. DOI: 10.1016/S0014-4835(66)80019-2.Bill A. Conventional and uveoscleral drainage of aqueous humour in the cynomolgus monkey (Macaca irus) at normal and high intraocular pressures. Exp Eye Res. 1966;5:45–54. DOI: 10.1016/S0014-4835(66)80019-2.Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res. 1971;12(3):275-281. DOI: 10.1016/0014-4835(71)90149-7.Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res. 1971;12(3):275-281. DOI: 10.1016/0014-4835(71)90149-7.Uusitalo H, Egorov E, Kaarniranta K et al. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta- analysis of two Phase IIIb clinical trials. Clin Ophthalmol. 2016 Mar15;10:445–454. DOI: 10.2147/OPTH.S91402.Uusitalo H, Egorov E, Kaarniranta K et al. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta- analysis of two Phase IIIb clinical trials. Clin Ophthalmol. 2016 Mar15;10:445–454. DOI: 10.2147/OPTH.S91402.Oh DJ, Martin JL, Williams AJ et al. Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2006;47(9):3887–3895. DOI: 10.1167/iovs.06-0036.Oh DJ, Martin JL, Williams AJ et al. Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2006;47(9):3887–3895. DOI: 10.1167/iovs.06-0036.Richter M, Krauss AH, Woodward DF, Lutjen-Drecoll E. Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide. Invest Ophthalmol Vis Sci. 2003;44(10):4419–4426. DOI: 10.1167/iovs.02-1281.Richter M, Krauss AH, Woodward DF, Lutjen-Drecoll E. Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide. Invest Ophthalmol Vis Sci. 2003;44(10):4419–4426. DOI: 10.1167/iovs.02-1281.Scherer WJ. A retrospective review of non-responders to latanoprost. J Ocul Pharmacol Ther. 2002;18(3):287–291. DOI: 10.1089/108076802760116205.Scherer WJ. A retrospective review of non-responders to latanoprost. J Ocul Pharmacol Ther. 2002;18(3):287–291. DOI: 10.1089/108076802760116205.Camras CB, Hedman K, US Latanoprost Study Group. Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma. J Glaucoma. 2003;12(6):466–469. DOI: 10.1097/00061198-200312000-00004.Camras CB, Hedman K, US Latanoprost Study Group. Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma. J Glaucoma. 2003;12(6):466–469. DOI: 10.1097/00061198-200312000-00004.Sakurai M, Higashide T, Takahashi M, Sugiyama K. Association between genetic polymorphisms of the prostaglandin F2a receptor gene and response to latanoprost. Ophthalmology. 2007;114(6):1039–1045. DOI: 10.1016/j.ophtha.2007.03.025.Sakurai M, Higashide T, Takahashi M, Sugiyama K. Association between genetic polymorphisms of the prostaglandin F2a receptor gene and response to latanoprost. Ophthalmology. 2007;114(6):1039–1045. DOI: 10.1016/j.ophtha.2007.03.025.Sakurai M, Higashide T, Takahashi M et al. Association between genetic polymorphisms of the prostaglandin F2a receptor gene and response to latanoprost in patients with glaucoma and ocular hypertension. Br J Ophthalmol. 2014;98(4):469–473. DOI: 10.1136/bjophthalmol-2013-304267.Sakurai M, Higashide T, Takahashi M et al. Association between genetic polymorphisms of the prostaglandin F2a receptor gene and response to latanoprost in patients with glaucoma and ocular hypertension. Br J Ophthalmol. 2014;98(4):469–473. DOI: 10.1136/bjophthalmol-2013-304267.Кукес В.Г., Сычев Д.А., Раменская Г.В. и др. Оценка активности изофермента цитохрома Р450 3А4 (CYP3A4) как реальная возможность персонализации фармакотерапии // Врач. 2008;(3):13-19. [Sychev DA, Ramenskaya GV, Kukes VG. Ocenka aktivnosti izofermenta citohroma R450 3A4 (CYP3A4) kak real’naya vozmozhnost’ personalizacii farmakoterapii. Vrach. 2008;(3):13–19. (In Russ).].Кукес В.Г., Сычев Д.А., Раменская Г.В. и др. Оценка активности изофермента цитохрома Р450 3А4 (CYP3A4) как реальная возможность персонализации фармакотерапии // Врач. 2008;(3):13-19. [Sychev DA, Ramenskaya GV, Kukes VG. Ocenka aktivnosti izofermenta citohroma R450 3A4 (CYP3A4) kak real’naya vozmozhnost’ personalizacii farmakoterapii. Vrach. 2008;(3):13–19. (In Russ).].Сычев Д.А., Раменская Г.В., Игнатьев И.В. и др. Клиническая фармакогенетика / Под редакцией В.Г. Кукеса, Н.П. Бочкова. – М.: ГЭОТАР-Медиа; 2007. – 248 с. [Sychev DA, Ramenskaya GV, Ignatiev IV et al. Klinicheskaya farmakogenetika. Ed by VG Kukes, NP Bochkov. Moscow: GEOTAR-Media; 2007. (In Russ).].Сычев Д.А., Раменская Г.В., Игнатьев И.В. и др. Клиническая фармакогенетика / Под редакцией В.Г. Кукеса, Н.П. Бочкова. – М.: ГЭОТАР-Медиа; 2007. – 248 с. [Sychev DA, Ramenskaya GV, Ignatiev IV et al. Klinicheskaya farmakogenetika. Ed by VG Kukes, NP Bochkov. Moscow: GEOTAR-Media; 2007. (In Russ).].Waldock A, Snape J, Graham CM. Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients. Br J Ophthalmol. 2000;84(7):710–713. DOI: 10.1016/s0002-9394(00)00916-8.Waldock A, Snape J, Graham CM. Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients. Br J Ophthalmol. 2000;84(7):710–713. DOI: 10.1016/s0002-9394(00)00916-8.

The authors declare that there are no conflicts of interest present.