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

Familial hypercholesterolemia 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 familial hypercholesterolemia 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 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, the exceptional molecular heterogeneity of familial hypercholesterolemia became obvious and, accordingly, the need to establish national spectra of mutations leading to the development of familial hypercholesterolemia was established. Researchers have moved from characterizing individual mutations to creating national registries and databases. Finally, research into the genetics of familial hypercholesterolemia has led to the emergence of new classes of cholesterol-lowering drugs. In Russia, molecular diagnostics of familial hypercholesterolemia has also undergone significant changes since the beginning of the study of familial hypercholesterolemia in 1987 and to the present, consideration of these changes formed the basis of this review.