RUDN Journal of MedicineRUDN Journal of MedicineВестник Российского университета дружбы народов. Серия: Медицина2313-02452313-0261Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University)4764710.22363/2313-0245-2025-29-4-454-469ADMYUSMEDICAL GENETICSМЕДИЦИНСКАЯ ГЕНЕТИКАReview ArticleBiological and psychological approach to familial hypercholesterolemiaБиологические и психологические аспекты семейной гиперхолестеренемииhttps://orcid.org/0000-0003-4685-50071840-3676TskhovrebovaLeyla V.ЦховребоваЛ. В.tskhovrebova-lv@rudn.ruhttps://orcid.org/0000-0003-0129-11562438-8880AghajanyanAnna V.АгаджанянА. В.tskhovrebova-lv@rudn.ruhttps://orcid.org/0000-0002-0873-80807000-7007BekoevaDiana D.БекоеваД. Д.tskhovrebova-lv@rudn.ruhttps://orcid.org/0009-0001-6522-15985787-6374KurevlevSergey V.КуревлевС. В.tskhovrebova-lv@rudn.ruRUDN UniversityРоссийский университет дружбы народовLopukhin Federal Research and Clinical Center of Physical-Chemical MedicineФедеральный научно-клиничесий центр физико-химической медицины им. акад. Ю.М. ЛопухинаLomonosov Moscow State UniversityМГУ имени М.В. Ломоносова18122025294MEDICAL GENETICSМЕДИЦИНСКАЯ ГЕНЕТИКА45446917122025Copyright ©; 2025, Tskhovrebova L.V., Aghajanyan A.V., Bekoeva D.D., Kurevlev S.V.Copyright ©; 2025, Цховребова Л.В., Агаджанян А.В., Бекоева Д.Д., Куревлев С.В.2025Tskhovrebova L.V., Aghajanyan A.V., Bekoeva D.D., Kurevlev S.V.Цховребова Л.В., Агаджанян А.В., Бекоева Д.Д., Куревлев С.В.https://creativecommons.org/licenses/by-nc/4.0https://journals.rudn.ru/medicine/article/view/47647

Relevance. Familial hypercholesterolemia (FH) is a monogenic hereditary disorder characterized by impaired lipid metabolism. The prevalence of FH in the general population averages 0.32% (95% CI: 0.26-0.39%). The disease can have both autosomal dominant and autosomal recessive inheritance patterns. Eight FH phenotypes associated with mutations in the LDLRAP1, PCSK9, APOA2, APOB, GHR, GSBS, EPHX2, and LDLR genes are known, which can lead to early manifestation of the pathology. The aim of this review is to comprehensively analyze current literature data on the molecular genetics, biological, and psychological aspects of FH. Analysis of signaling pathways in FH revealed three clusters of genes and their encoded proteins responsible for the following processes: assembly, remodeling, and clearance of plasma lipoproteins (genes: LDLR, LDLRAP1, VLDLR, NPC1L1, APOC1, LPA, CETP, MTTP, APOB, PCSK9); cholesterol metabolism (gene: PPP1R17);regulation of plasma lipoprotein particle levels (gene: ANGPTL3). The proteins PCSK9, APOB, and MTTP were identified as key elements (central hubs) of these metabolic networks. The PPP1R17 protein is involved in the mechanisms of long-term depression, a form of synaptic plasticity. Furthermore, the literature describes an association of FH with five other genes: ABCG5, ABCG8, STAP1, CYP7A1, LIPA, and PNPLA5. Conclusion. Thus, for the early diagnosis and effective management of patients with FH, it is necessary to consider not only the expanded spectrum of associated genes and proteins but also the psychological state of patients, particularly their levels of anxiety, depression, and stress.

Семейная гиперхолестеринемия (СГ) - это моногенное наследственное заболевание с нарушением метаболизма липидов. Распространенность СГ в общей популяции в среднем составляет 0,32% (95% ДИ: 0,26-0,39%). Заболевание может иметь как аутосомно-доминантный, так и аутосомно-рецессивный типы наследования. Известно 8 фенотипов СГ, связанных с мутациями в генах LDLRAP1, PCSK9, APOA2, APOB, GHR, GSBS, EPHX2 и LDLR, которые могут приводить к раннему проявлению патологии. Целью данного обзора является комплексное исследование данных современной литературы по молекулярно-генетическим, биологическим и психологическим аспектам СГ. Анализ сигнальных путей при СГ выявил три кластера генов и кодируемых ими белков, ответственных за следующие процессы: сборку, ремоделирование и клиренс липопротеинов плазмы (гены: LDLR, LDLRAP1, VLDLR, NPC1L1, APOC1, LPA, CETP, MTTP, APOB, PCSK9); метаболизм холестерина (ген: PPP1R17); регуляцию уровня частиц липопротеинов плазмы (ген: ANGPTL3). Белки PCSK9, APOB и MTTP идентифицированы как ключевые элементы (центральные узлы) этих метаболических сетей. Белок PPP1R17 вовлечен в механизмы долговременной депрессии, формы синаптической пластичности. Кроме того, в литературе описана ассоциация СГ с пятью другими генами: ABCG5, ABCG8, STAP1, CYP7A1, LIPA и PNPLA5. Таким образом, для ранней диагностики и эффективного ведения пациентов с СГ необходимо учитывать не только расширенный спектр ассоциированных генов и белков, но и психологическое состояние пациентов, в частности уровень их тревожности, депрессии и стресса.

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