PARP1 V762A: от каталитического дефекта до патологии

В обзоре обобщены данные о связи замены Val762Ala в белке PARP (poly(ADP-ribose) polymerase), снижающей его каталитическую активность, с риском развития широкого спектра заболеваний: злокачественных, аутоиммунных, нейродегенеративных и сердечнососудистых. Показано, что характер этой связи зависит от типа патологии, этнической принадлежности, тканевого контекста и наличия дополнительных факторов (инфекция Helicobacter pylori, курение и взаимодействие с факторами репарации). Снижение активности PARP1 усугубляет дефект репарации ДНК и, следовательно, повышает риск онкологических заболеваний, связанных с хронической генотоксической нагрузкой (рак желудка, шейки матки, пищевода, мочевого пузыря). Напротив, при патологиях с доминированием окислительного стресса и воспаления (бронхиальная астма, тиреоидит Хашимото, ишемическая болезнь сердца, глиома) минорный аллель Ala762 выступает как защитный фактор, ограничивая PARP1-зависимое истощение НАД⁺ и ослабляя NF‑κB-опосредованную воспалительную реакцию. Имеющиеся данные свидетельствуют о том, что замена Val762Ala является контекст-зависимым модификатором риска, оценка которого требует комплексного подхода с учетом этноса, типа заболевания, воздействия внешних факторов и полигенных взаимодействий

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