Familial dysbetalipoproteinemia: genetic modifiers

Abstract

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic genetically based hyperlipidemia. The aim was to evaluate genetic drivers, contributing to FD using genetic data, n=4594. 24 lipid-related genes and 40 variants included in the hypertriglyceridemia genetic risk score were analyzed by NGS. The genetic basis of FD was identified in 67 patients, for 76.1% of whom was established FD. The autosomal recessive form contributed 74.5%, and the autosomal dominant FD was predominated by the carriage of APOE p.Arg154Cys (61.5%). In addition, 13.7% of FD patients were carriers of two or more causal variants in lipid-related genes (3 carriers of ε2ε1 APOE, 2 – of ε2ε2/LDLR, 1 – of ε2ε2/LPL, 1 – of p.Arg154Cys and compound heterozygous for two LPL variants). Polygenic hypertriglyceridemia was found in 41.7% of FD patients. The results demonstrate the diversity of genetic drivers in the overall structure of FD.