Анализ вариантов в генах липидного обмена у лиц молодого возраста 25–44 лет с контрастными уровнями холестерина липопротеинов низкой плотности

Рост распространенности гиперхолестеринемии липопротеинов низкой плотности (ЛПНП) и связанных с ней заболеваний среди молодежи является серьезной проблемой для многих стран. Цель исследования – идентифицировать редкие функционально значимые варианты в кодирующих областях и прилегающих сайтах сплайсинга генов, ассоциированных с повышенным уровнем холестерина ЛПНП (ХС ЛПНП), у мужчин и женщин 25–44 лет.
Методы. Включенная в исследование популяционная выборка была распределена по децилям на основе концентрации ХС ЛПНП. В исследование включили 146 человек с уровнем ХС ЛПНП ˂ 2,1 ммоль/л, входящих в первый дециль и 158 человек с уровнем ХС ЛПНП ≥ 4,2 ммоль/л, входящих в последний дециль. Выполнено таргетное высокопроизводительное секвенирование.
Результаты. В выборке молодых людей у 0,07 % обследованных уровень ХС ЛПНП превышал 8,5 ммоль/л, у 0,13 % обследованных находился в пределах 6,5–8,4 ммоль/л, у 2,25 % – в пределах 5,0–6,4 ммоль/л. В нашем исследовании обследованные с уровнем ХС ЛПНП, соответствующим первому и последнему децилю, различались по спектру вариантов в генах липидного обмена. Функционально значимые варианты, связанные с развитием гиперхолестеринемии ЛПНП, выявлены у молодых людей с уровнем ХС ЛПНП ≥ 4,2 ммоль/л в кодирующих областях генов LDLR и APOB, а также в генах ABCA1, LCAT, LIPA, LIPC, LPA.
Заключение. Идентифицированы редкие функционально значимые варианты в кодирующих областях и прилегающих сайтах сплайсинга генов, ассоциированных с повышенным уровнем холестерина ЛПНП, у мужчин и женщин в молодом возрасте.

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