kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2020-9-2-38-44kpccz-713Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESПолиморфизм гена APOA5 у пациентов с первичной гиперлипидемиейPolymorphism of the APOA5 gene in patients with primary hyperlipidemiahttps://orcid.org/0000-0002-0897-5473МихайловаС. В.MikhailovaS. V.

Михайлова Светлана Владимировна - кандидат биологических наук, научный сотрудник, исполняющая обязанности заведующей лабораторией молекулярной генетики человека.

Пр. Академика Лаврентьева, 10, Новосибирск, 630090

Mikhailova Svetlana V. - D, Head of the Laboratory of Human Molecular Genetics.

10, Ac. Lavrentieva ave., Novosibirsk, 630090

https://orcid.org/0000-0002-0403-545XИванощукД. Е.IvanoshchukD. E.

Иванощук Динара Евгеньевна - младший научный сотрудник лаборатории молекулярной генетики человека.

Пр. Академика Лаврентьева, 10, Новосибирск, 630090

Ivanoshchuk Dinara E. - junior researcher at the Laboratory of Human Molecular Genetics.

10, Ac. Lavrentieva ave., Novosibirsk, 630090

https://orcid.org/0000-0002-8828-0259ШироковаН. С.ShirokovaN. S.

Широкова Нина Сергеевна - студент Института медицины и психологии В. Зельмана.

Ул. Пирогова, 2, Новосибирск, 630090

Shirokova Nina S. - student at the V. Zelman Institute for Medicine and Psychology.

2, Pirogova St., Novosibirsk, 630090

https://orcid.org/0000-0001-6108-1025ШахтшнейдерЕ. В.ShakhtshneiderE. V.

Шахтшнейдер Елена Владимировна - кандидат медицинских наук, ведущий научный сотрудник, заведующая сектором изучения моногенных форм распространенных заболеваний человека.

Пр. Академика Лаврентьева, 10, Новосибирск, 630090

Shakhtshneider Elena V. - PhD, MD, leading researcher, Head of the Division of Monogenic Forms of Human Common Disease.

10, Ac. Lavrentieva ave., Novosibirsk, 630090

2117409@mail.ruФедеральное государственное бюджетное научное учреждение Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияFederal Research Center Institute of Cytology and Genetics, Siberian Branch ofRussian Academy ofSciencesRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования Новосибирский национальный исследовательский государственный университетРоссияNovosibirsk State UniversityRussian Federation202024062020923844Copyright © Михайлова С.В., Иванощук Д.Е., Широкова Н.С., Шахтшнейдер Е.В., 20202020Михайлова С.В., Иванощук Д.Е., Широкова Н.С., Шахтшнейдер Е.В.Mikhailova S.V., Ivanoshchuk D.E., Shirokova N.S., Shakhtshneider E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/713Цель

Цель. Анализ генетического полиморфизма гена APOA5 среди пациентов европеоидного происхождения с семейной гиперхолестеринемией.

Материалы и методы

Материалы и методы. Выборка из 43 неродственных пациентов европеоидного происхождения с семейной гиперхолестеринемией (СГХС) сформирована с использованием диагностического критерия DutchLipidClinicNetwork. Таргетное секвени-рование геномной ДНК выполнено с помощью набора NimbleGenSeqCapEZChoicekit на пиросеквенаторе RocheJuniorGS (Roche, Швейцария).

Результаты

Результаты. У пациентов с СГХС выявлены восемь замен в гене APOA5 - rs2075291, rs3135506, rs2072560, rs2266788, rs3135507, rs34089864, rs619054, rs651821, -для которых ранее показана ассоциация с дислипидемией, а также одна ранее не описанная замена Ala169Asp, которая может менять заряд сайта связывания белка с липидными каплями в гепатоцитах. Не выявлено различий в частоте внутригенного гаплотипа ApoA5*2, для которого ранее показана ассоциация с повышенным уровнем триглицеридов, между пациентами c СГХС и популяцией.

Заключение

Заключение. Генетические варианты APOA5, распространенные у пациентов с СГХС, могут участвовать в формировании патологического фенотипа дислипидемии, однако для более точной оценки их вклада целесообразно проводить дифференциацию пациентов с СГХС по уровню триглицеридов.

Aim

Aim. To study APOA5 genetic polymorphism in Caucasoid patients with familial hypercholesterolemia.

Methods

Methods. Sample of patient with familial hypercholesterolemia (43 unrelated Caucasoid persons) was formed using Dutch Lipid Clinic Network Criteria. Targeted sequencing of genome DNA was performed by NimbleGen SeqCap EZ Choice kit on pyrosequencer Roche Junior GS (Roche, Switzerland).

Results

Results. In patients with familial hypercholesterolemia, 8 substitutions were identified in the APOA5 gene: rs2075291, rs3135506, rs2072560, rs2266788, rs3135507, rs34089864, rs619054, and rs651821, that are known to be associated with dyslipidemia. One novel substitution Ala169Asp was found. It is responsible for changing the charge of a domain for lipid droplets binding in the APOA5 protein. There were no differences in the frequencies of the ApoA5*2 intragenic haplotype, which has been recently reported to be associated with an increased triglyceride levels in patients with familial hypercholesterolemia and the population.

Conclusion

Conclusion. Genetic variants ofAPOA5, common in patients with familial hypercholesterolemia, may be involved in the formation of the pathological phenotype of dyslipidemia. However, a more accurate assessment oftheir contribution is required to differentiate patients with familial hypercholesterolemia according to their triglycerides level.

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