Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia.
Apolipoprotein B-100
/ genetics
Cardiovascular Diseases
/ blood
Cholesterol, LDL
/ blood
Female
Genotype
Humans
Hyperlipoproteinemia Type II
/ blood
Male
Middle Aged
Multifactorial Inheritance
/ genetics
Mutation
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Proprotein Convertase 9
/ genetics
Receptors, LDL
/ genetics
Risk Factors
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
25
05
2020
revised:
31
07
2020
accepted:
03
08
2020
pubmed:
10
8
2020
medline:
21
8
2021
entrez:
10
8
2020
Statut:
ppublish
Résumé
Autosomal-dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB, and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1985 controls. The 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (P < .05) and healthy controls (P < .001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL-C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a six-SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients.
Substances chimiques
APOB protein, human
0
Apolipoprotein B-100
0
Cholesterol, LDL
0
LDLR protein, human
0
Receptors, LDL
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
457-467Informations de copyright
© 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
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