Генетические факторы риска развития нежелательных лекарственных реакций

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.

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