fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУfcmedicine-113Research ArticleСтатьиСВЯЗЬ ПОЛИМОРФИЗМОВ ГЕНОВ МЕТАБОЛИЗМА КАЛЬЦИЯ С РИСКОМ ТЯЖЕЛОЙ КАЛЬЦИФИКАЦИИ КСЕНОАОРТАЛЬНЫХ БИОПРОТЕЗОВ КЛАПАНОВ СЕРДЦА, ИМПЛАНТИРОВАННЫХ В МИТРАЛЬНУЮ ПОЗИЦИЮRS13290979 POLYMORPHISM WITHIN NOTCH1 GENE IS ASSOCIATED WITH SEVERE BIOPROSTHETIC MITRAL VALVE CALCIFICATIONПонасенкоА. В.PonasenkoANASTASIA V.noemail@neicon.ruКутихинА. Г.KutikhinANTON G.noemail@neicon.ruХуторнаяМ. В.KhutornayaMARIA V.noemail@neicon.ruРутковскаяН. В.RutkovskayaNATALIA V.noemail@neicon.ruЦепокинаА. В.TsepokinaANNA V.noemail@neicon.ruКондюковаН. В.KondyukovaNATALIA V.noemail@neicon.ruЮжалинА. Е.YuzhalinARSENIY E.noemail@neicon.ruБарбарашЛ. С.BarbarashLEONID S.noemail@neicon.ruФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian FederationКафедра онкологии, Оксфордский институт радиационной онкологии, Оксфордский университетРоссияCRUK/MRC Oxford Institute for Radiation Oncology, University of OxfordRussian Federation201830122018341221Copyright © Понасенко А.В., Кутихин А.Г., Хуторная М.В., Рутковская Н.В., Цепокина А.В., Кондюкова Н.В., Южалин А.Е., Барбараш Л.С., 20182018Понасенко А.В., Кутихин А.Г., Хуторная М.В., Рутковская Н.В., Цепокина А.В., Кондюкова Н.В., Южалин А.Е., Барбараш Л.С.Ponasenko A.V., Kutikhin A.G., Khutornaya M.V., Rutkovskaya N.V., Tsepokina A.V., Kondyukova N.V., Yuzhalin A.E., Barbarash L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/113

Цель. Тяжелая кальцификация ксеноаортальных биопротезов клапанов сердца, имплантированных в митральную позицию, часто ведет к функциональной недостаточности биопротеза и является важной проблемой в сердечно-сосудистой хирургии. К сожалению, до настоящего времени практически отсутствуют работы, посвященные генетической восприимчивости к тяжелой кальцификации таких биопротезов. Данная работа была проведена с целью оценить связь полиморфизмов генов метаболизма кальция с риском тяжелой кальцификации ксеноаортальных биопротезов клапанов сердца, имплантированных в митральную позицию. Материалы и методы. В исследование бы-ло включено 124 пациента, подвергшихся операции по замене митрального клапана (62 с функциональной недостаточностью протезного клапана вследствие его тяжелой кальцификации и 62 с нормальным функциональным состоянием биопротеза). Всего было оценено восемь полиморфизмов в пяти генах: rs13290979 (ген NOTCH1), rs731236 и rs2228570 (ген VDR), rs1042636 (ген CASR), rs3134069, rs2073618, rs3102735 (ген OPG) и rs1801197 (ген CALCR). Генотипирование проводилось по технологии TaqMan (аллель-специфичная полимеразная цепная реакция с флюоресцентной детекцией результата в реальном времени). Статистический анализ проводился в программе SNPStats с расчетом отношения шансов согласно пяти моделям наследственности (кодоминантной, доминантной, рецессивной, сверхдоминантной и лог-аддитивной), Поправка на множественные сравнения проводилась с использованием средней доли ложных отклонений гипотез (false discovery rate, FDR).Результаты. Генотип G/G полиморфизма rs13290979 гена NOTCH1, кодирующего одно- именный рецептор, был ассоциирован с почти трехкратно повышенным риском тяжелой кальцификации ксеноаортальных биопротезов клапанов сердца, имплантированных в митральную позицию, в сравнении с генотипами A/A и A/G. Генотипы других изученных полиморфизмов не были статистически значимо ассоциированы с вероятностью возникновения данной патологии.Заключение. Полиморфизмы генов метаболизма кальция (в частности, гена NOTCH1) могут обусловливать генетическую восприимчивость к тяжелой кальцификации биопротезов клапанов сердца.

Aim. Bioprosthetic mitral valves frequently undergo severe calcification causing bioprosthetic valve failure, an urgent problem in cardiovascular surgery. However, no research have been performed on genetic susceptibility to severe bioprosthetic mitral valve calcification. Here we assessed whether inherited variation in genes of calcium metabolism is associated with severe bioprosthetic mitral valve calcification. Materials and Methods. We recruited 124 consecutive patients who underwent mitral valve replacement surgery. We assessed eight polymorphisms within the five genes: rs13290979 (NOTCH1 gene), rs731236 and rs2228570 (VDR gene), rs1042636 (CASR gene), rs3134069, rs2073618, rs3102735 (OPG gene) and rs1801197 (CALCR gene). Genotyping was carried out in 96-well format using the TaqMan SNP genotyping assay. Statistical analysis was performed utilizing the SNPStats software, with the calculation of the odds ratio according to codominant, dominant, recessive, overdominant, and log-additive models of inheritance. Adjustment for multiple comparisons was conducted using false discovery rate.Results. G/G genotype of the rs13290979 polymorphism within the NOTCH1 gene was associated with 2.75-fold increased risk of severe bioprosthetic mitral valve calcification compared to the A/A and A/G genotypes. Other genotypes did not show a significant association with this condition.Conclusions. Polymorphisms within the calcium metabolism genes (e.g., NOTCH1 gene) may be associated with severe bioprosthetic mitral valve calcification.

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The authors declare that there are no conflicts of interest present.