Analysis Of The Ldlr, Apob, Pcsk9 And Ldlrap1 Genes Variability In Patients With Familial Hypercholesterolemia In West Siberia Using Targeted High Throughput Resequencing

Shakhtshneider, E.; Ivanoshchuk, D.; Орлов, П. С.; Тимощенко, О. В.; Воевода, М. И.

doi:10.1016/j.atherosclerosis.2019.06.883

Cited by 5 publications

(4 citation statements)

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“…Most of these variants were unique but some LDLR variants occurred in several unrelated patients: p.Cys68Phe, p.Pro196Arg, p.Cys318Trp, p.Tyr375Asp and p.Ile566Phe. Of 35 variants previously described in the literature [ 6 , 7 , 8 , 9 , 10 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] only for the Russian population, six variants were also found in this study. Most of these variants were also unique, except for variant LDLR -p.Cys160Gly, that was found in six unrelated patients.…”

Section: Resultssupporting

confidence: 71%

“…The search strategy described above yielded 665 citations; 474 remained after duplicate removal. After the analysis of the abstracts referring to genetic testing or LDLR , APOB and PCSK9 variants in FH patients, 27 articles were selected, of which 25 contained data on the LDLR , APOB , and PCSK9 variants, including three of previously published articles by our group [ 6 , 7 , 8 , 9 , 10 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. These articles describe 91 causal variants of LDLR gene, one variant of APOB, and one variant of PCSK9 ( Figure 1 , Table A1 , Table A2 and Table A3 in Appendix A ).…”

Section: Resultsmentioning

confidence: 99%

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The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Мешков

Ершова

Киселева

et al. 2021

Genes

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Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

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Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Мешков

Ершова

Киселева

et al. 2021

Genes

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“…All missense variants were heterozygous. Some of the identified variants (Cys352Tyr, Cys340Phe, and Leu401His) have been described in patients with familial hypercholesterolemia in Russia [26][27][28][29][30]. The variant most common in our participations-rs121908038-was found in three unrelated families (six subjects total).…”

Section: Ldlrmentioning

confidence: 77%

“…Molecular genetic research on familial hypercholesterolemia in Russia has been conducted for more than 30 years in different regions of the country [29]. It is worth mentioning some variants of the LDLR gene that not only occur in most regions of Russia but are also the most common variants of this gene: rs121908038 and rs761954844 [28][29][30][31][32]57]. Additionally, these variants have been found in populations of Northern and Central Europe (rs121908038) and in populations of Central and Eastern Europe, Southeast Asia, and North America (rs761954844) [40].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)

Shakhtshneider

Ivanoshchuk

Тимощенко

et al. 2021

JPM

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The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the LDLR promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the LDLR gene were identified in 19 probands (73.1% of all variants identified in probands); in three probands (11.5%), pathogenic variants were found in the APOB gene; and in four probands (15.4%), rare, clinically significant variants were identified in genes LPL, SREBF1, APOC3, and ABCG5. In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.

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

Zakharova,

Mandelstam,

Bogoslovskaya

et al. 2024

Medical academic journal

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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.

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Analysis Of The Ldlr, Apob, Pcsk9 And Ldlrap1 Genes Variability In Patients With Familial Hypercholesterolemia In West Siberia Using Targeted High Throughput Resequencing

Cited by 5 publications

References 0 publications

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)

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

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