Фармакогенетические эффекты однонуклеотидных полиморфизмов, влияющих на метаболизм антиретровирусных препаратов

Введение. Определение фармакогенетических особенностей при назначении антиретровирусной терапии (АРТ) является важной составляющей персонализированного лечения ВИЧ-позитивных пациентов. АРТ может приводить к развитию различных нежелательных явлений (НЯ). Эффективность терапии и возникновение НЯ могут быть обусловлены генетической предрасположенностью, которую следует учитывать при выборе схемы АРТ. Некоторые известные аллели (HLAB*57:01 и UGT1A1*28) связаны с развитием НЯ и прекращением приема АРТ. В настоящее время важной клинической задачей является расширение спектра клинически значимых генетических тестов.

Цель. В обзоре представлены данные об эффектах генетических полиморфизмов, влияющих на переносимость АРТ. Проведен анализ данных об однонуклеотидных полиморфизмах (SNP) в генах, участвующих в метаболизме и транспорте АРТ. Результаты обзора предполагается использовать для разработки основанных на полимеразной цепной реакции методик определения аллелей риска в европейской популяции.

Материалы и методы. Проанализированы данные 46 публикаций. При анализе учитывались данные о частотах аллелей SNP в европейской популяции.

Результаты. Выбрано несколько наиболее перспективных SNP. Полиморфизмы в генах ABCC4 (rs1751034, rs3742106) и ABCC10 (rs9349256, rs2125739) связаны с повышенным риском нарушения функции почек, обусловленного более высокой концентрацией в плазме крови препарата тенофовир. Показана эффективность одновременного исследования SNP в этих генах и CYP24A1 (rs2248359) как потенциального маркера нефротоксичности. Полиморфизм в гене CYP2B6 (rs3745274) связан с повышением концентрации эфавиренца в плазме крови, повышенным риском гепатотоксичности и развития НЯ со стороны ЦНС. SNP в CYP2B6, CYP2A6 (rs28399433) и CYP3A4 (rs4646437) следует исследовать вместе, поскольку все три SNP ассоциированы с высоким риском развития НЯ.

Заключение. Описанные аллели SNP являются новыми диагностическими маркерами, которые могут быть использованы при назначении АРТ. Для оценки их клинической значимости и перспектив практического применения у пациентов с ВИЧ-инфекцией в России требуется проведение дополнительных исследований.

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