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

А Н Мешков ,Vasily Ramensky,Evgenia Zotova,Т А Рожкова ,О В Курилова ,А В Блохина ,А В Петухова ,П П Малышев ,Valentin V Makarov ,S M Yudin ,А С Лимонова ,В В Кухарчук ,Alexsandra I Akinshina ,А А Букаева ,Sergey I Mitrofanov ,Daria A Kashtanova ,Valeriya M Mikova ,О П Скирко ,Е А Сотникова ,Ekaterina A Snigir ,А В Киселева ,Zukhra B Khasanova ,M S Pokrovskaya ,А И Ершова ,Anastasia A Zharikova ,S А Boytsov ,Mikhail G Divashuk ,О М Drapkina

doi:10.3390/genes12010066

Abstract

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.

Highlights

After the analysis of the abstracts referring to genetic testing or LDLR, APOB and
In our study we performed genetic testing of 595 unrelated patients with Familial hypercholesterolemia (FH), of which six patients demonstrated the phenotype of homozygous FH (HoFH) and the rest had clinical features of HeFH
Target sequencing was performed for 401 patients and whole genome sequencing was performed for 405 patients

Summary

Introduction

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein (LDL) cholesterol levels causing premature atherosclerotic cardiovascular disease [1]. Mutations in one of the three genes (low-density lipoprotein receptor gene (LDLR), apolipoprotein B gene (APOB) and proprotein convertase subtilisin/kexin type 9 gene (PCSK9)) cause both HeFH and HoFH, and these genes account for the vast majority of genetically confirmed cases of FH [1]. The aim of this study is to present data on the spectrum of the LDLR, APOB and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, and to perform an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian FH patients

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Conclusion