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

Jean-Philippe Drouin-Chartier, Jean-Charles Hogue, André J Tremblay, Jean Bergeron, Benoît Lamarche, Patrick Couture, Jean-Philippe Drouin-Chartier, Jean-Charles Hogue, André J Tremblay, Jean Bergeron, Benoît Lamarche, Patrick Couture

Abstract

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 μg/mL; P < 0.0001). There were no correlations between apoB-48 and PCSK9 plasma levels in both controls (ρ = 0.06, P = 0.5) and HeFH subjects (ρ = 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.

Trial registration: NCT02225340 .

Keywords: Apolipoprotein B-48; Atherosclerosis; Familial hypercholesterolemia; PCSK9.

Figures

Fig. 1
Fig. 1
Relative increase in concentrations of plasma PCSK9 and plasma apoB-48 in HeFH and HoFH subjects vs. control subjects. Values are presented as mean ± standard deviation. Ctrls: controls; HeFH: heterozygotes for familial hypercholesterolemia; HoFH: homozygotes for familial hypercholesterolemia; apo: apolipoprotein; PCSK9: proprotein convetase subtilisin/kexin type 9. †P < 0.05 vs. controls. ‡P < 0.05 vs. HeFH
Fig. 2
Fig. 2
Correlations between plasma apoB-48 and PCSK9 concentrations in control subjects and HeFH subjects. HeFH: heterozygotes for familial hypercholesterolemia; apo: apolipoprotein; PCSK9: proprotein convertase subtilisin/kexin type 9. NS: non-significant
Fig. 3
Fig. 3
Radar plot presenting the associations among fasting apolipoprotein B-48 levels, PCSK9 concentrations and various plasma lipids in control subjects and HeFH subjects. Radar lines represent Spearman’s correlation coefficient. Continuous lines represent apoB-48 concentrations. Dashed lines represent PCSK9 concentrations. Circles represent HeFH subjects. Squares represent control subjects. Filled marks identify significant association (P < 0.05), and white-filled marks represent non-significant association. Apo: apolipoprotein; C: cholesterol; HeFH: heterozygotes for familial hypercholesterolemia; TG: triglyceride

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