The <i>LDLR</i>, <i>APOB</i>, and <i>PCSK9</i> Variants of Index Patients with Familial Hypercholesterolemia in Russia

• Main Authors: Alexey Meshkov, Alexandra Ershova, Anna Kiseleva, Evgenia Zotova, Evgeniia Sotnikova, Anna Petukhova, Anastasia Zharikova, Pavel Malyshev, Tatyana Rozhkova, Anastasia Blokhina, Alena Limonova, Vasily Ramensky, Mikhail Divashuk, Zukhra Khasanova, Anna Bukaeva, Olga Kurilova, Olga Skirko, Maria Pokrovskaya, Valeriya Mikova, Ekaterina Snigir, Alexsandra Akinshina, Sergey Mitrofanov, Daria Kashtanova, Valentin Makarov, Valeriy Kukharchuk, Sergey Boytsov, Sergey Yudin, Oxana Drapkina
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Genes
• Subjects: familial hypercholesterolemia; Russian; whole genome sequencing; <i>LDLR</i>; <i>APOB</i>; <i>PCSK9</i>
• Online Access: https://www.mdpi.com/2073-4425/12/1/66

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 <i>LDLR</i>, <i>APOB</i>, and <i>PCSK9</i> 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 <i>LDLR</i>, <i>APOB</i>, and <i>PCSK9</i> 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 <i>LDLR</i>, <i>APOB</i> and <i>PCSK9</i> 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 <i>LDLR</i>, 14 variants in <i>APOB,</i> and 23 variants in <i>PCSK9</i>. 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.