This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipid Clinic Network (DLCN) and Simon Broome score between 2017 and 2020. Two techniques were used to identify mutations: multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The mutation rate was 37.7%, i.e., 23 patients with mutations were identified, of which 7 subjects had pathogenic mutations and 16 had polymorphisms. Moreover, 10 variants of the low-density lipoprotein receptor (LDLR) gene were identified in 22 patients, i.e., one variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in six patients, and one variant of the apolipoprotein B (APOB) gene in three patients. Of the LDLR gene variants, four were LDLR pathogenic mutations (c.81C > G, c.502G > A, c.1618G > A mutations in exon 2, exon 4, exon 11, and exon 13-15 duplication). The PCSK9 and APOB gene variants were benign mutations. The pathogenic LDLR mutations were significant predictors of the new cardiovascular events, and the time interval for new cardiovascular events occurrence was significantly decreased, compared to FH patients without mutations. In total, 12 variants were identified, with four pathogenic variants identified in the LDLR gene, whereas 62.3% of the study population displayed no pathological mutations.
Keywords: cardiovascular events; familial hypercholesterolemia; molecular genetic; pathogenic mutations.