Роль полиморфизма гена SELE при инфаркте миокарда с подъемом сегмента ST

   Ишемическая болезнь сердца представляет собой важную медико-социальную проблему. Наиболее тяжелой формой заболевания, с поражением всех слоев сердечной мышцы, считается инфаркт миокарда с подъемом сегмента ST (ИМпST). Одним из диагностических критериев дисфункции эндотелия при инфаркте миокарда является уровень sE-селектина – молекулы клеточной адгезии, осуществляющей рекрутинг нейтрофилов и индукцию нейтрофильного воспаления. В настоящем исследовании изучен интронный полиморфизм (rs5353, rs3917412, rs1534904) гена SELE, кодирующего Е-селектин, у пациентов с ИМпST. Проанализированы две выборки: пациенты с ИМпST (n = 74) и популяционная выборка г. Томска (n = 136). По частотам генотипов rs5353 в гене SELE зарегистрированы статистически значимые различия между пациентами и контрольной выборкой (p = 0.004). Генотип СС является рисковым по отношению к ИМпST (OR = 6.93, CI:95 % (1.84–26.04), χ² = 8.69, p = 0.002). Проанализированные маркеры не изучались ранее при сердечно-сосудистых заболеваниях и вообще редко привлекались к ассоциативным исследованиям; в ведущих базах данных отсутствует информация об ассоциациях этих маркеров с заболеваниями. Вместе с тем все три варианта по классификации RegulomeDB относятся к функциональному классу 1f и, соответственно, с высокой вероятностью обладают регуляторным потенциалом относительно не только гена SELE, но и других генов близлежащего региона. Анализ функциональной значимости изученных маркеров показал наличие более обширного, чем один ген, региона, корегулируемого данными нуклеотидными заменами. Выявленная в настоящем исследовании ассоциация rs5353 с ИМпST еще раз подтверждает вовлеченность гена SELE в развитие сердечно-сосудистых заболеваний. Не исключено, что опосредованно (через системы воспаления, иммунного ответа и репарации ДНК) весь этот регион генома может быть вовлечен в патогенез сердечно-сосудистых заболеваний.

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