Research output: Contribution to journal › Article › peer-review
Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia. / Blokhina, Anastasia V.; Ershova, Alexandra I.; Kiseleva, Anna V. et al.
In: International Journal of Molecular Sciences, Vol. 25, No. 23, 12651, 12.2024.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia
AU - Blokhina, Anastasia V.
AU - Ershova, Alexandra I.
AU - Kiseleva, Anna V.
AU - Sotnikova, Evgeniia A.
AU - Zharikova, Anastasia A.
AU - Zaicenoka, Marija
AU - Vyatkin, Yuri V.
AU - Ramensky, Vasily E.
AU - Kutsenko, Vladimir A.
AU - Garbuzova, Elizaveta V.
AU - Divashuk, Mikhail G.
AU - Litinskaya, Olga A.
AU - Pokrovskaya, Maria S.
AU - Shalnova, Svetlana A.
AU - Meshkov, Alexey N.
AU - Drapkina, Oxana M.
PY - 2024/12
Y1 - 2024/12
N2 - Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare APOE variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare APOE variants and FD. Genetic data from 4720 subjects were used to identify rare APOE 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 APOE 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 APOE variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, p = 0.034) and variants of uncertain significance (median 1.38 mmol/L, p = 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 APOE variants may advance our understanding of the genetic basis of FD and underscore the importance of APOE gene sequencing in patients with lipid metabolism disorders.
AB - Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare APOE variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare APOE variants and FD. Genetic data from 4720 subjects were used to identify rare APOE 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 APOE 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 APOE variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, p = 0.034) and variants of uncertain significance (median 1.38 mmol/L, p = 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 APOE variants may advance our understanding of the genetic basis of FD and underscore the importance of APOE gene sequencing in patients with lipid metabolism disorders.
KW - APOE
KW - apolipoprotein E
KW - autosomal dominant
KW - dyslipidemia
KW - familial dysbetalipoproteinemia
KW - hyperlipoproteinemia type III
KW - pathogenicity
KW - phenotype/genotype correlation
KW - remnant lipoproteins
KW - triglycerides
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85212237038&origin=inward&txGid=89442ee1c30cba30eb953d21590e9c8f
UR - https://www.mendeley.com/catalogue/f0bf4614-e76c-34a0-82e3-632c883b94d7/
U2 - 10.3390/ijms252312651
DO - 10.3390/ijms252312651
M3 - Article
C2 - 39684364
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 23
M1 - 12651
ER -
ID: 61279078