The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels

Background: Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B-48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a large cohort of genetically defined FH heterozygotes (HeFH) and homozygotes (HoFH). Methods: A total of 118 HeFH, 6 HoFH, and 117 controls were included in the study. Plasma PCSK9 and apoB-48 concentrations were measured in the fasting state. Results: Plasma PCSK9 and apoB-48 levels were higher in FH subjects compared with controls (PCSK9: HoFH: 642. 6 +/- 246.9 vs. HeFH: 324.9 +/- 119.8 vs. controls: 194.5 +/- 65.9 ng/mL, P < 0.0001; apoB-48: HoFH: 14.71 +/- 4.36 vs. HeFH: 6.55 +/- 4.24 vs. controls: 3.03 +/- 2.07 mu g/mL; P < 0.0001). There were no correlations between apoB-48 and PCSK9 plasma levels in both controls (rho = 0.06, P = 0.5) and HeFH subjects (rho = 0.07, P = 0.4). Multiple linear regression analysis showed that the FH status was the only independent factor associated with apoB-48 levels, contributing to 28.7% of the variance (P < 0.0001). Conclusions: These data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels.