Прогностическая значимость носительства аллельных вариантов генов, контролирующих систему гемостаза, и их сочетания с традиционными факторами риска в раннем развитии ишемической болезни сердца

Цель. Определить прогностическую значимость носительства аллельных вариантов генов факторов свертывания крови и их сочетания с негенетическими факторами риска (ФР): курение, артериальная гипертония (АГ), гиперхолестеринемия (ГХС), ожирение (Ож), в раннем развитии ишемической болезни сердца (ИБС), в т. ч. инфаркта миокарда (ИМ) у больных ИБС.
Материал и методы. Обследованы 977 мужчин в возрасте 20–55 лет: 375 больных ИБС, в т. ч.: 186 – без ИМ, 189 – с ИМ в анамнезе и 602 человека без сердечно-сосудистых заболеваний (ССЗ). Проведен анализ полиморфизма генов тромбоцитарных рецепторов гликопротеина Ia (C807T) и гликопротеина IIIa (PLA1/PLA2); полиморфизма генов, кодирующих белки свертывающей и противосвертывающей систем крови: полиморфизм R353Q VII фактора, V34L XIII фактора свертывания крови и инсерционно-делеционный полиморфизм 4G/5G ингибитора активатора плазминогена 1 типа, а также их сочетания с традиционными ФР: курение, АГ, ГХС, Ож. Для определения аллельных вариантов исследуемых генов использовали метод полимеразной цепной реакции (ПЦР) с анализом длины рестриктных фрагментов, аллельспецифичной ПЦР и метод ПЦР в режиме «реального времени».
Результаты. С повышенным риском формирования ИБС ассоциировался генотип ТТ гена GPIa (p=0,0001) (OR=10,2). С уменьшением риска развития ИБС ассоциировались генотип LL FXIII (p=0,03) (OR=0,48) и генотип QQ FVII свертывания крови (p=0,01) (OR=0,12), а сочетание L-аллеля гена FXIII с Q аллелем FVII ассоциировалось с уменьшением риска развития ИМ как осложнения ИБС (p=0,03) (OR=0,33). Анализ сочетаний генотипов с традиционными ФР показал, что PLA2/PLA2 генотип GPIIIa у больных с ГХС повышает риск развития ИМ у больных ИБС (p=0,01) (OR=6,0).
Заключение. В алгоритм генетической диагностики предрасположенности к раннему развитию ИБС могут быть включены: полиморфизм C807T гена гликопротеина Ia, PLA1/PLA2 гена гликопротеина IIIa, V34L гена А-субъединицы фактора XIII свертывания крови и R304Q гена фактора VII свертывания крови. В исследовании не нашло подтверждение негативное влияние полиморфизма 4G/5G гена PAI-1 на развитие ИБС и ИМ.

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