cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2025-4607UUGLZKcardiovascular-4607Research ArticleГЕНЕТИКА В КАРДИОЛОГИИGENETICS IN CARDIOLOGYГенетические причины вариабельности липидного спектра при семейной гиперхолестеринемииGenetic causes of lipid profile variability in familial hypercholesterolemiahttps://orcid.org/0000-0002-5375-7328МихайлинаВ. И.MikhailinaV. I.

Михайлина Виктория Игоревна — м.н.с. отдела персонализированной диагностики, терапии и профилактики атеросклеротических сердечно-сосудистых заболеваний Института персонализированной терапии и профилактики

Петроверигский пер., д. 10, стр. 3, Москва, 101990

Petroverigsky Lane, 10, bld. 3, Moscow, 101990

spandex2007@mail.ruhttps://orcid.org/0000-0002-2798-9811ЗайченокаМ.ZaychenokaM.

Зайченока Мария — аспирант

Институтский пер., д. 9, г. Долгопрудный, Московская область, 141701

Institutskiy Lane, 9, Dolgoprudny, 141701

marija.zaicenoka@gmail.comhttps://orcid.org/0000-0003-4765-8021КиселеваА. В.KiselevaA. V.

Киселева Анна Витальевна — к.б.н., в.н.с., руководитель лаборатории молекулярной генетики Института персонализированной терапии и профилактики

Петроверигский пер., д. 10, стр. 3, Москва, 101990

Petroverigsky Lane, 10, bld. 3, Moscow, 101990

https://orcid.org/0000-0001-5989-6233МешковА. Н.MeshkovА. N.

Мешков Алексей Николаевич — д.м.н., руководитель Института персонализированной терапии и профилактики  ; помощник генерального директора по научной и клинической работе ФГБУ «НМИЦ кардиологии имени академика Е.И. Чазова» Минздрава России; профессор кафедры биохимической генетики и наследственных болезней обмена веществ ФГБНУ «МГНЦ им. академика Н.П. Бочкова» Министерства науки и высшего образования Российской Федерации; профессор кафедры общей и медицинской генетики МБФФГАОУ ВО «РНИМУ им. Н. И. Пирогова» Минздрава России 

Петроверигский пер., д. 10, стр. 3, Москва, 101990,

ул. Академика Чазова, д. 15А, Москва, 121552,

ул. Москворечье, д. 1, Москва, 115522,

ул. Островитянова, д. 1, Москва, 117513

 

Petroverigsky Lane, 10, bld. 3, Moscow, 101990,

Akademika Chazova str., 15A, Moscow, 121552,

Moskvorechye str., 1, Moscow, 115522,

Ostrovitianova str., 1, Moscow, 117513

https://orcid.org/0000-0002-4453-8430ДрапкинаО. М.DrapkinaО. M.

Драпкина Оксана Михайловна — д.м.н., профессор, академик РАН, директор

Петроверигский пер., д. 10, стр. 3, Москва, 101990

Petroverigsky Lane, 10, bld. 3, Moscow, 101990

ODrapkina@gnicpm.ruФГБУ "Национальный медицинский исследовательский центр терапии и профилактической медицины" Минздрава РоссииРоссияNational Medical Research Center for Therapy and Preventive MedicineRussian FederationФГАОУ ВО "Московский физико-технический институт (национальный исследовательский университет)"РоссияMoscow Institute of Physics and Technology (National Research University)Russian FederationФГБУ "Национальный медицинский исследовательский центр терапии и профилактической медицины" Минздрава России; ФГБУ "Национальный медицинский исследовательский центр кардиологии им. акад. Е. И. Чазова" Минздрава России; ФГБНУ "Медико-генетический научный центр им. акад. Н. П. Бочкова" Министерства науки и высшего образования Российской Федерации; ФГАОУ ВО "Российский национальный исследовательский медицинский университет им. Н. И. Пирогова" Минздрава РоссииРоссияNational Medical Research Center for Therapy and Preventive Medicine; Chazov National Medical Research Center of Cardiology; Bochkov Research Center for Medical Genetics; Pirogov Russian National Research Medical UniversityRussian Federation202508022026241246074607Copyright © Михайлина В.И., Зайченока М., Киселева А.В., Мешков А.Н., Драпкина О.М., 20262026Михайлина В.И., Зайченока М., Киселева А.В., Мешков А.Н., Драпкина О.М.Mikhailina V.I., Zaychenoka M., Kiseleva A.V., Meshkov А.N., Drapkina О.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/4607

Семейная гиперхолестеринемия (СГХС) — одно из самых частых моногенных заболеваний в России, которое в большинстве случаев обусловлено наличием причинных вариантов в генах LDLR, APOB, PCSK9. СГХС характеризуется выраженной гиперхолестеринемией с рождения и ранним развитием коронарного атеросклероза и ишемической болезни сердца. Однако за последние годы накопились данные о том, что фенотип генетически подтвержденных больных СГХС может варьировать от классического пациента с ишемической болезнью сердца до пациентов без атеросклероза вовсе. Широкий спектр фенотипических проявлений заболевания обусловлен неполной пенетрантностью и/или вариабельной экспрессивностью вариантов в причинных генах. В настоящем обзоре продемонстрированы основные генетические причины развития СГХС и дополнительные генетические факторы, влияющие на вариабельность липидных показателей (дополнительные редкие и частые варианты в генах, связанных с нарушениями липидного обмена). Знания о вариабельности липидного спектра при СГХС помогут практикующим врачам эффективнее использовать методы генетической диагностики, оценивать риск развития осложнений и персонализировано подбирать лечение.

Familial hypercholesterolemia (FH) is one of the most common monogenic diseases in Russia, most often related to causal variants in the LDLR, APOB, and PCSK9 genes. FH is characterized by severe hypercholesterolemia from birth and the early development of coronary atherosclerosis and coronary artery disease. However, in recent years, there is evidence indicating that the phenotype of genetically confirmed FH patients can vary from those with coronary artery disease to those without atherosclerosis. The wide profile of phenotypic manifestations is due to incomplete penetrance and/or variable expressivity of variants in the causal genes. This review demonstrates the main genetic causes of FH and additional genetic factors influencing lipid variability (additional rare and common variants in genes associated with lipid metabolism disorders). Understanding lipid profile variability in FH will help practicing physicians more effectively use genetic diagnostic methods, assess the risk of complications, and personalize treatment.

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