1. Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia
- Author
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Claudia Mischung, Elisabeth Steinhagen-Thiessen, Thomas Bobbert, Frieda Bardey, Ursula Kassner, Ilja Demuth, Johannes Helmuth, Thomas Grenkowitz, Lorenz Rieck, Joachim Spranger, and Lars Bertram
- Subjects
Male ,0301 basic medicine ,Multifactorial Inheritance ,medicine.medical_specialty ,Genotype ,Apolipoprotein B ,Single-nucleotide polymorphism ,Familial hypercholesterolemia ,030105 genetics & heredity ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Gastroenterology ,Hyperlipoproteinemia Type II ,03 medical and health sciences ,Risk Factors ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic variability ,Genetics (clinical) ,low-density lipoprotein cholesterol ,Mutation ,familial hypercholesterolemia ,biology ,business.industry ,PCSK9 ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,030104 developmental biology ,Receptors, LDL ,Cardiovascular Diseases ,Apolipoprotein B-100 ,LDL receptor ,biology.protein ,Kexin ,Female ,lipids (amino acids, peptides, and proteins) ,Proprotein Convertase 9 ,business ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
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 1,985 controls. 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
- Published
- 2020
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