Hyperalphalipoproteinemia, as observed in patients who are either homozygous or heterozygous for cholesteryl
ester transfer protein (CETP) deficiency, has been shown to be associated with striking changes in apolipoprotein size distribution,
namely, of high-density lipoprotein (HDL) and HDL-like particles. We compared the effect of varying degrees
of CETP activity on the HDL apolipoprotein profile in Caucasian CETP-deficient subjects and following pharmacological
decrease in CETP activity, using Size Exclusion Chromatography followed by Reverse Phase Protein Array (SEC RPA).
The main HDL-associated apolipoproteins (Apo), i.e. ApoA-I, ApoA-II, ApoC-I, and ApoC-III, co-eluted with the HDL
peak. The presence of a HDL-like peak migrating between the ApoB-LDL and ApoA-I-HDL was identified in a Caucasian
patient with homozygosity for a point mutation in exon 2 of the CETP gene (c.109 C > T) resulting in a premature
termination codon (R37X) and complete CETP deficiency. This HDL-like peak was not observed either in healthy volunteers
treated with the CETP modulator dalcetrapib, patients heterozygous for the same mutation, or in patients heterozygous
with G165X mutations. SEC RPA offers the possibility to investigate the distribution of a large number of apolipoproteins
simultaneously under non-denaturing separation in normal and dyslipidemic subjects. This is only limited by the
availability of antibodies against specific apolipoproteins to be investigated.
Keywords: Cholesteryl ester transfer protein, dalcetrapib, high-density lipoprotein, reverse phase protein array, scavenger receptor class B1, size exclusion chromatography, torcetrapib, apolipoprotein, hyperalphalipoproteinemia, ELISA
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