Биомедицинские и кандидатные SN P-маркеры для хронопатологий могут достоверно изменять сродство ТАТА -связывающего белка к промоторам генов человека

Компьютерный анализ миллионов неаннотированных SNPs (Single Nucleotide Polymorphisms) из проекта «1 000 геномов» может ускорить поиск биомедицинских SNP-маркеров. Анализ при помощи Web-сервиса SNP_ TATA_Comparator SNPs сайтов связывания ТАТА -связывающего белка (ТВР) сочетали с поиском хронопатологий по ключевым словам так, чтобы биохимические маркеры хронопатологий соответствовали изменениям экспрессии генов, содержащих эти SNPs. Для промоторов 14 генов человека в районе [– 70; – 20] (район доказанных сайтов связывания ТВР) были найдены биомедицинские и кандидатные SNP-маркеры нарушений циркадного ритма, которые могут достоверно (Z-тест) изменять сродство ТВР к этим промоторам. В их числе: rs17231520, rs569033466 (хронопатологии печени); rs35036378 (хронопатология поведенческой активности); rs549858786 (хронопатология экспрессии IL1B при ревматоидном артрите); rs563207167, rs11557611, rs5505 (хронопатологии баланса «опухоль – хозяин», кровяного давления и репродуктивной системы); rs1143627 (циркадность диагностики и терапии биполярного расстройства); rs16887226, rs544850971 (неустойчивость к эндотоксинам из- за дисбаланса циркадной и иммунной систем); rs367732974, rs549591993 (циркадность обострений сердечной недостаточности); rs563763767 (циркадность случаев инфаркта миокарда); rs2276109, rs572527200 (циркадность приступов астмы); rs34223104, rs563558831 и rs10168 (циркадные оптимумы терапии метотрексатом и циклофосфамидом); rs397509430, rs33980857, rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, rs34166473 (циркадность синдрома беспокойных ног и нейросенсорной тугоухости). Проверка этих 32 SNP-маркеров по медицинским стандартам может способствовать предиктивно-превентивной персонифицированной медицине.

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