Микросомальный белок-переносчик триглицеридов: молекулярная генетика, функциональные механизмы и клиническое значение

Цель настоящей работы – провести комплексный обзор структурно-функциональной организации гена MTTP и кодируемого им микросомального белка‑переносчика триглицеридов (МБПТ), охарактеризовать его патогенные варианты и описать молекулярные механизмы их действия. МБПТ является ключевым регулятором липидного обмена, необходимым для сборки и секреции apoB‑содержащих липопротеинов в гепатоцитах и энтероцитах. Биаллельные патогенные варианты гена MTTP вызывают абеталипопротеинемию – редкое жизнеугрожающее заболевание с прогрессирующими неврологическими и офтальмологическими осложнениями. Распространенные варианты гена ассоциированы с различными метаболическими нарушениями. Проведен обзор литературы с анализом структуры и механизмов альтернативного сплайсинга гена MTTP, доменной организации белка МБПТ, его взаимодействия с протеин‑дисульфид‑изомеразой, и некоторых патогенных вариантов этого гена на основе опубликованных функциональных исследований и клинических данных. Углубленное понимание молекулярных механизмов дисфункции МБПТ необходимо для корректной интерпретации результатов генетического тестирования, прогнозирования клинического фенотипа, проведения дифференциальной диагностики и разработки персонализированных терапевтических стратегий при абеталипопротеинемии и ассоциированных с ней нарушениях.

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