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

Abstract Background and aims 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 . Methods 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). Results 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). Conclusions 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.