cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-1120Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEW ARTICLESФармакогенетика ингибиторов ГМГ-КоА-редуктазы (статинов): возможности индивидуализации терапии на основе генотипаPharmacogenetics of HMG-CoA reductase inhibitors (statins): perspectives of individualized, genotype-based therapyСычевД. А.SychevD. A.СеменовА. В.SemenovA. V.alex_semenov@rambler.ruРаменскаяГ. В.RamenskayaG. V.ИгнатьевИ. В.IgnatyevI. V.ПауковС. В.PaukovS. V.КукесВ. Г.KukesV. G.Московская медицинская академия им. И.М. Сеченова; Институт клинической фармакологии ФГУ «Научный центр экспертизы средств медицинского применения» Росздрава. МоскваI.M. Sechenov Moscow Medical Academy; Clinical Pharmacology Institute, Scientific Center for Medical Agents Expertise, Ministry of Health of the Russian Federation. MoscowМосковская медицинская академия им. И.М. СеченоваI.M. Sechenov Moscow Medical AcademyИнститут клинической фармакологии ФГУ «Научный центр экспертизы средств медицинского применения» Росздрава. МоскваClinical Pharmacology Institute, Scientific Center for Medical Agents Expertise, Ministry of Health of the Russian Federation. Moscow20062002200651100104Copyright © Сычев Д.А., Семенов А.В., Раменская Г.В., Игнатьев И.В., Пауков С.В., Кукес В.Г., 20062006Сычев Д.А., Семенов А.В., Раменская Г.В., Игнатьев И.В., Пауков С.В., Кукес В.Г.Sychev D.A., Semenov A.V., Ramenskaya G.V., Ignatyev I.V., Paukov S.V., Kukes V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/1120

Преимущества статинов в лечении ишемической болезни сердца хорошо известны, однако их эффективность имеет существенные индивидуальные различия. Отчасти это объясняется генетическим полиморфизмом. Фармакологический ответ пациента на статины может зависеть от полиморфизма генов белков, ответственных за фармакокинетику статинов, за механизм их действия, а также белков, участвующих в патогенезе атеросклероза. Носители аллельных вариантов генов CYP2C9, CYP3A4, CYP2D6, MDR-1, ОАТР-С могут демонстрировать более выраженное гиполипидемическое действие и/или нежелательные лекарственные реакции вследствие изменения фармакокинетических параметров. Полиморфизмы генов HMGCR и CETP, кодирующих основные мишени статинов, также могут оказывать значимое влияние на их эффективность. Ряд белков, участвующих в патогенезе атеросклероза, (APO-E, ABCG5/G8, CYP7A1) имеют аллельные варианты, что может приводить к измененному ответу на терапию статинами. Для оптимизации терапии статинами необходимо большое количество исследований по изучению влияния полиморфизмов различных генов на риск развития неблагоприятных сердечно-сосудистых событий на фоне их длительного применения.

Statins’ efficacy in coronary heart disease treatment is well known, but their effectiveness is a subject to substantial individual differences. Partially, it is explained by genetic polymorphism. Individual pharmacological response to statins might depend on genetic polymorphism of the proteins determining statins’ pharmacokinetics and their mechanism of action, as well as proteins involved into atherosclerosis pathogenesis. People with alleles of CYP2C9, CYP3A4, CYP2D6, MDR-1, ОАТР-С genes could demonstrate more prominent hypolipidemic effects and/or more adverse events, due to modified pharmakokinetics. HMGCR and CETP polymorphism of the genes coding principal «targets» for statins, might affect the latter’s effectiveness as well. Some proteins, involved into atherosclerosis pathogenesis (APO-E, ABCG5/G8, CYP7A1) have allele variants explaining different answers to statin treatment. To optimize long-term statin therapy, more studies on genetic polymorphism links to adverse cardiovascular events, are needed.

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