Lipid-lowering response in subjects with the p.(Leu167del) mutation in the APOE gene

• Published in: Atherosclerosis Vol. 282; pp. 143 - 147
• Main Authors: Bea, Ana M., Lamiquiz-Moneo, Itziar, Marco-Benedí, Victoria, Mateo-Gallego, Rocio, Pérez-Calahorra, Sofía, Jarauta, Estíbaliz, Martín, César, Cenarro, Ana, Civeira, Fernando
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.03.2019
• Subjects: Adult; Alleles; APOE; Apolipoproteins E - genetics; Case-Control Studies; Cholesterol, LDL - genetics; Ezetimibe - administration & dosage; Familial hypercholesterolemia; Female; Gene Deletion; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hyperlipoproteinemia Type II - genetics; Leucine - genetics; Lipid Metabolism; Lipid-lowering treatment; Male; Middle Aged; Mutation; p.(Leu167del); Receptors, LDL - genetics; Retrospective Studies; p.(Leu167del); Lipid-lowering treatment; APOE; Familial hypercholesterolemia
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2019.01.024

The aim of this work was to compared the effect of lipid lowering drugs among familial hypercholesterolemia (FH) subjects with a functional mutation in LDLR (LDLR FH) and FH with the p.(Leu167del) mutation in APOE. We retrospectively selected all adults with the p.(Leu167del) mutation on lipid-lowering treatment (n = 22) attending the Lipid Unit at the Hospital Miguel Servet. Age and sex matched LDLR FH from the same Unit were randomly selected as a control group (n = 44). The mean percentage reduction in LDLc was significantly higher in the p.(Leu167del) carriers (−52.1%) than in the LDLR FH (−39.7%) (p = 0.040) when on high intensity statins. Similar differences between groups were observed in non-HDLc −49.4% and −36.4%, respectively (p = 0.030). Subjects with p.(Leu167del) mutation have a higher lipid-lowering response to statins with or without ezetimibe than LDLR FH. This supports the use of genetics for a more efficient management of FH. •The p.(Leu167del) mutation in APOE has been described as a new cause of familial hypercholesterolemia (FH).•The p.(Leu167del) carriers were on significantly lower dose of statin than LDLR FH.•The p.(Leu167del) carriers had higher lipid-lowering effect to statins than LDLR FH.•Our results support the use of genetics for a more efficient management of FH.