Biological and psychological approach to familial hypercholesterolemia

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Abstract

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.

About the authors

Leyla V. Tskhovrebova

RUDN University; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine

Author for correspondence.
Email: tskhovrebova-lv@rudn.ru
ORCID iD: 0000-0003-4685-5007
SPIN-code: 1840-3676
Moscow, Russian Federation

Anna V. Aghajanyan

RUDN University

Email: tskhovrebova-lv@rudn.ru
ORCID iD: 0000-0003-0129-1156
SPIN-code: 2438-8880
Moscow, Russian Federation

Diana D. Bekoeva

Lomonosov Moscow State University

Email: tskhovrebova-lv@rudn.ru
ORCID iD: 0000-0002-0873-8080
SPIN-code: 7000-7007
Moscow, Russian Federation

Sergey V. Kurevlev

RUDN University

Email: tskhovrebova-lv@rudn.ru
ORCID iD: 0009-0001-6522-1598
SPIN-code: 5787-6374
Moscow, Russian Federation

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