TY - JOUR
T1 - Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia
AU - Huijgen, R.
AU - Fouchier, S. W.
AU - Denoun, M.
AU - Hutten, B. A.
AU - Vissers, M. N.
AU - Lambert, G.
AU - Kastelein, J. J. P.
PY - 2012
Y1 - 2012
N2 - The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible. Mutation carriers with a LDL-C level below the 75th percentile (called "FH low") were selected, as well as those with LDL-C above the 90th percentile (called "FH high"). Relatives who tested negative for the mutation were the "controls." PCSK9 plasma levels were assessed in 267 individuals who did not receive cholesterol-lowering treatment at the time of the study. Mean PCSK9 plasma levels (95% CI) were lower in the FH-low group compared with the FH-high group [152 (137-167) ng/ml vs. 186 (165-207) ng/ml, P = 0.010] and the control group [177 (164-190) ng/ml, P = 0.013]. Mean PCSK9 levels did not statistically differ between the FH-high and control groups (P = 0.50).jlr Plasma PCSK9 levels are positively associated with LDL-C levels in FH patients and might contribute to the phenotypic severity in this disorder. Therefore, the results of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.-Huijgen, R., S. W. Fouchier, M. Denoun, B. A. Hutten, M. N. Vissers, G. Lambert, and J. J. P. Kastelein. Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia. J. Lipid Res. 2012. 53: 979-983
AB - The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible. Mutation carriers with a LDL-C level below the 75th percentile (called "FH low") were selected, as well as those with LDL-C above the 90th percentile (called "FH high"). Relatives who tested negative for the mutation were the "controls." PCSK9 plasma levels were assessed in 267 individuals who did not receive cholesterol-lowering treatment at the time of the study. Mean PCSK9 plasma levels (95% CI) were lower in the FH-low group compared with the FH-high group [152 (137-167) ng/ml vs. 186 (165-207) ng/ml, P = 0.010] and the control group [177 (164-190) ng/ml, P = 0.013]. Mean PCSK9 levels did not statistically differ between the FH-high and control groups (P = 0.50).jlr Plasma PCSK9 levels are positively associated with LDL-C levels in FH patients and might contribute to the phenotypic severity in this disorder. Therefore, the results of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.-Huijgen, R., S. W. Fouchier, M. Denoun, B. A. Hutten, M. N. Vissers, G. Lambert, and J. J. P. Kastelein. Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia. J. Lipid Res. 2012. 53: 979-983
U2 - https://doi.org/10.1194/jlr.P023994
DO - https://doi.org/10.1194/jlr.P023994
M3 - Article
C2 - 22375030
SN - 0022-2275
VL - 53
SP - 979
EP - 983
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 5
ER -