Gene Mutation in Patients with Familial Hypercholesterolemia and Response to Alirocumab Treatment—A Single-Centre Analysis

<b>Background</b>: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by significantly elevated levels of low-density lipoprotein (LDL) cholesterol, which plays a major role in the progression of atherosclerosis and leads to a heightened risk of premature atherosclerotic cardiovascular disease. <b>Methods</b>: We have carried out an observational study on a group of 17 patients treated at the Outpatient Lipid Clinic from 2019 to 2024. <b>Result</b>: The most frequent mutation observed was found in the <i>LDL receptor (LDLR)</i> gene, which was identified in ten patients (58.8%). Five patients were identified to have a mutation in the <i>apolipoprotein B (APOB)</i> gene, whereas two patients had two points mutations, one in the <i>LDLR</i>, and the other in the <i>APOB</i> gene. The average age of patients with <i>LDLR</i> mutation was 54.8 (12.3); for <i>APOB</i> mutation it was 61.4 (9.3) and for patients with two points mutation it was 61.5 (14.8). The study results showed that at Week 12, individuals with <i>LDLR</i>-defective heterozygotes who were given alirocumab 150 mg every two weeks experienced a 63.0% reduction in LDL cholesterol levels. On the other hand, individuals with <i>APOB</i> heterozygotes experienced a 59% reduction in LDL cholesterol levels. However, in patients with double heterozygous for mutations in <i>LDLR</i> and <i>APOB</i> genes, there was a hyporesponsiveness to alirocumab, and the reduction in LDL-C was only by 23% in two individuals. <b>Conclusions</b>: In patients with a single mutation, there was a greater response to treatment with alirocumab in contrast to patients with double heterozygous mutation, who did not respond to treatment with PCSK9 inhibitors.