Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia

Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare <i>APOE</i> variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare <i>APOE</i> variants and FD. Genetic data from 4720 subjects were used to identify rare <i>APOE</i> variants and investigate their pathogenicity for autosomal dominant FD. We observed 24 variants in 86 unrelated probands. Most variants were unique (66.7%). Five identified <i>APOE</i> variants (p.Glu63ArgfsTer15, p.Gly145AlafsTer97, p.Lys164SerfsTer87, p.Arg154Cys, and p.Glu230Lys) are causal for autosomal dominant FD. One of them (p.Lys164SerfsTer87) was described for the first time. When we compared clinical data, it was found that carriers of pathogenic or likely pathogenic <i>APOE</i> variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, <i>p</i> = 0.034) and variants of uncertain significance (median 1.38 mmol/L, <i>p</i> = 0.036). For the first time, we estimated the expected prevalence of causal variants for autosomal dominant FD in the population sample: 0.27% (one in 619). Investigating the spectrum of <i>APOE</i> variants may advance our understanding of the genetic basis of FD and underscore the importance of <i>APOE</i> gene sequencing in patients with lipid metabolism disorders.

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Journal
International Journal of Molecular Sciences
Published
2024-11-25
DOI
https://doi.org/10.3390/ijms252312651
Citations
5
Primary Topic
Lipoproteins and Cardiovascular Health
Type
article
Field-Weighted Citation Impact
2.86
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article

Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia

М.Г. Дивашук, А. И. Ершова, А. В. Блохина, Е. А. Сотникова et al.
5 citations
International Journal of Molecular Sciences
Lipoproteins and Cardiovascular Health
2.86
article

Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia

М.Г. Дивашук, А. И. Ершова, А. В. Блохина, Е. А. Сотникова, Marija Zaicenoka, Vladimir Aleksandrovich Kutsenko, Yuri V. Vyatkin, Alexey N. Meshkov, Anastasia A. Zharikova, Svetlana Anatolievna Shalnova, O. А. Litinskaya, Anna V. Kiseleva, M. S. Pokrovskaya, Vasily Ramensky, E. V. Garbuzova, Oxana M. Drapkina
article en
5 citations

Abstract

Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare <i>APOE</i> variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare <i>APOE</i> variants and FD. Genetic data from 4720 subjects were used to identify rare <i>APOE</i> variants and investigate their pathogenicity for autosomal dominant FD. We observed 24 variants in 86 unrelated probands. Most variants were unique (66.7%). Five identified <i>APOE</i> variants (p.Glu63ArgfsTer15, p.Gly145AlafsTer97, p.Lys164SerfsTer87, p.Arg154Cys, and p.Glu230Lys) are causal for autosomal dominant FD. One of them (p.Lys164SerfsTer87) was described for the first time. When we compared clinical data, it was found that carriers of pathogenic or likely pathogenic <i>APOE</i> variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, <i>p</i> = 0.034) and variants of uncertain significance (median 1.38 mmol/L, <i>p</i> = 0.036). For the first time, we estimated the expected prevalence of causal variants for autosomal dominant FD in the population sample: 0.27% (one in 619). Investigating the spectrum of <i>APOE</i> variants may advance our understanding of the genetic basis of FD and underscore the importance of <i>APOE</i> gene sequencing in patients with lipid metabolism disorders.

International Journal of Molecular SciencesVol. 25(23)
Novosibirsk State University (RU), Lomonosov Moscow State University (RU), Pirogov Russian National Research Medical University (RU), National Research Center for Preventive Medicine (RU), Ministry of Health of the Russian Federation (RU), Research Centre for Medical Genetics (RU), All-Russian Scientific Research Institute of Food Biotechnology (RU), National Medical Research Center of Cardiology (RU)
Good health and well-being
Openalex Percentile: Top 9%
Lipoproteins and Cardiovascular Health
2.86
DOIOpen Access PDFOpenAlex
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