APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia - Université Sorbonne Paris Nord Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia

Sybil Charrière
Anne Philippi
  • Fonction : Auteur

Résumé

Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant hypercholesterolemia (ADH) or associated with elevated triglyceride levels in familial combined hyperlipidemia (FCHL). Rare APOE variants are known in ADH and FCHL. We explored the APOE molecular spectrum in a French ADH/FCHL cohort of 5743 unrelated probands. The sequencing of LDLR, PCSK9, APOB, and APOE revealed 76 carriers of a rare APOE variant, with no mutation in LDLR, PCSK9, or APOB. Among the 31 APOE variants identified here, 15 are described in ADH, 10 in FCHL, and 6 in both probands. Five were previously reported with dyslipidemia and 26 are novel, including 12 missense, 5 synonymous, 2 intronic, and 7 variants in regulatory regions. Sixteen variants were predicted as pathogenic or likely pathogenic, and their carriers had significantly lower polygenic risk scores (wPRS) than carriers of predicted benign variants. We observed no correlation between LDL-C levels and wPRS, suggesting a major effect of APOE variants. Carriers of p.Leu167del were associated with a severe phenotype. The analysis of 11 probands suggests that carriers of an APOE variant respond better to statins than carriers of a LDLR mutation. Altogether, we show that the APOE variants account for a significant contribution to ADH and FCHL.
Fichier principal
Vignette du fichier
ijms-23-05792-v3.pdf (1.56 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03772585 , version 1 (18-10-2022)

Licence

Paternité

Identifiants

Citer

Yara Abou Khalil, Oriane Marmontel, Jean Ferrières, François Paillard, Cécile Marie Yelnik, et al.. APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. International Journal of Molecular Sciences, 2022, 23 (10), ⟨10.3390/ijms23105792⟩. ⟨hal-03772585⟩
54 Consultations
42 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More