Molecular diagnostics of familial hypercholesterolemia in Russia: yesterday, today and tomorrow



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Abstract

Familial hypercholesterolemia (FH) is a severe hereditary disease leading to the development of atherosclerosis and its complications in the form of angina pectoris, myocardial infarction, cerebral stroke, or even leading to sudden death. Since the description of the disease, the concept of it has undergone significant evolution. First, it became clear that the prevalence of this disease was significantly higher than originally thought (1:300 for heterozygous FH and not as 1:500 as estimated earlier). Secondly, it has been established that it is not based on the pathology of the low-density lipoprotein receptor (LDLR) gene alone, but includes at least four monogenic forms (defects of the APOB, PCSK9, ARH genes) and may also have a multigenic nature. Thirdly, with the development of DNA analysis methods from the initially available Southern hybridization to next generation DNA sequencing (NGS), the exceptional molecular heterogeneity of FH became obvious and, accordingly, the need to establish national spectra of mutations leading to the development of FH was established. Researchers have moved from characterizing individual mutations to creating national registries and databases. Finally, research into the genetics of FH has led to the emergence of new classes of cholesterol-lowering drugs. In Russia, molecular diagnostics of FH has also undergone significant changes since the beginning of the study of FH in 1987 and to the present, consideration of these changes formed the basis of this review.

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About the authors

Faina Mikhailovna Zakharova

Institute of Experimental Medicine

Author for correspondence.
Email: fzakharova@mail.ru
ORCID iD: 0000-0002-9558-3979
SPIN-code: 9699-5744

Ph.D., senior researcher of the Department of Molecular Genetics 

Russian Federation, 12, Acad. Pavlov Street, 197376, St. Petersburg

Mikhail Yurievich Mandelstam

Institute of Experimental Medicine

Email: amitinus@mail.ru
ORCID iD: 0000-0002-7135-3239
SPIN-code: 1893-9417

Ph.D, leading researcher of the Department of Molecular

Russian Federation, 12, Acad. Pavlov Street, 197376, St. Petersburg

Tatiana Yurievna Bogoslovskaya

Institute of Experimental Medicine

Email: ktu17@yandex.ru
ORCID iD: 0000-0002-9480-1073
SPIN-code: 8406-6162

Ph.D., researcher of the Department of Molecular Genetics

Russian Federation, 12, Acad. Pavlov Street, 197376, St. Petersburg

Vadim Borisovich Vasiliev

Institute of Experimental Medicine

Email: vadim@biokemis.ru
ORCID iD: 0000-0002-9707-262X
SPIN-code: 8298-1469

Ph.D., M.D., professor, head of the Department of Molecular Genetics

Russian Federation, 12, Acad. Pavlov Street, 197376, St. Petersburg

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