safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2022-10-1-48-64safetyrisk-245Research ArticleФАРМАКОГЕНЕТИКАPHARMACOGENETICSГенетические факторы риска развития нежелательных лекарственных реакцийGenetic Risk Factors for Adverse Drug Reactionshttps://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Сычев Дмитрий Алексеевич, член-корр. РАН, д-р мед. наук, профессор

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Dmitry A. Sychev, Corr. Member of the RAS, Dr. Sci. (Med.), Professor

2/1/1 Barrikadnaya St., Moscow 125993

rmapo@rmapo.ruhttps://orcid.org/0000-0003-3091-7904ЧерняеваМ. С.ChernyaevaM. S.

Черняева Марина Сергеевна, канд. мед. наук

ул. Маршала Тимошенко, д. 19, стр. 1А, Москва, 121359

Marina S. Chernyaeva, Cand. Sci. (Med.)

19, bld. 1A Marshal Timoshenko St., Moscow 121359

doctor@cherniaeva.ruhttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

Остроумова Ольга Дмитриевна, д-р мед. наук, профессор

ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Olga D. Ostroumova, Dr. Sci. (Med.), Professor

2/1/1 Barrikadnaya St., Moscow 1259938/2 Trubetskaya St., Moscow 2119991

ostroumova.olga@mail.ruФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationФедеральное государственное бюджетное учреждение дополнительного профессионального образования «Центральная государственная медицинская академия» Управления делами Президента Российской ФедерацииРоссияCentral State Medical AcademyRussian FederationФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияRussian Medical Academy of Continuous Professional Education; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation2022090220221014864Copyright © Сычев Д.А., Черняева М.С., Остроумова О.Д., 20222022Сычев Д.А., Черняева М.С., Остроумова О.Д.Sychev D.A., Chernyaeva M.S., Ostroumova O.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/245

Применение лекарственных средств (ЛС) в ряде случаев может быть сопряжено с развитием нежелательных реакций (НР), в том числе лекарственно-индуцированных заболеваний (ЛИЗ), что ведет к повышению уровней заболеваемости, смертности и/или к возникновению симптомов, вынуждающих пациента обратиться за медицинской помощью или приводящих к госпитализации. Причиной развития НР могут быть изменения в генотипе пациента, которые влекут за собой нарушения фармакологического ответа. Цель работы: анализ и систематизация данных литературы о генетических факторах риска, обусловливающих развитие НР или вызывающих ЛИЗ. Показано, что полиморфизм генов, кодирующих ферменты метаболизма ЛС (CYP, UGT, NAT, TPMT, EPHX, GST и др.) или переносчики (транспортеры) ЛС (P-gp, BCRP, MRP, OATP, OCT и др.), может изменять фармакокинетику ЛС, влияя на их активность. Полиморфизм генов RYR1, CACNA1S, MT-RNR1, VKORC1 и др., кодирующих рецепторы-мишени ЛС, и гена HLA лейкоцитарного антигена человека может влиять на фармакодинамику ЛС, модифицируя мишени ЛС или изменяя чувствительность биологических путей к фармакологическим эффектам ЛС. Изменение фармакокинетики и фармакодинамики ЛС могут стать причиной развития ЛИЗ и других НР. Использование фармакогенетических тестов позволит персонализированно подойти к лечению пациента и предпринять превентивные меры для предотвращения или своевременного выявления потенциально возможных НР на фоне проводимой терапии. Перед назначением некоторых ЛС клиницистам целесообразно использовать информацию по их дозированию на основе фармакогенетических тестов, размещенную на официальных сайтах исследовательской сети фармакогеномики (Pharmacogenomics Research Network, PGRN), базы данных по фармакогеномике (Pharmacogenomics Knowledgebase, PharmGKB), а также клинические рекомендации Консорциума по внедрению клинической фармакогенетики (Clinical Pharmacogenetics Implementation Consortium, CPIC). Результаты проводимых в настоящее время клинических исследований влияния полиморфизма генов на безопасность ЛС в ближайшем будущем позволят повысить персонализацию выбора фармакотерапии и предотвратить развитие многих НР, в том числе ЛИЗ.

The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs.

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