QUANTITATIVE AND COMPOSITIONAL CHANGES IN HIGH-DENSITY-LIPOPROTEIN SUBCLASSES IN PATIENTS WITH VARIOUS GENOTYPES OF CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY
H. Chiba et al., QUANTITATIVE AND COMPOSITIONAL CHANGES IN HIGH-DENSITY-LIPOPROTEIN SUBCLASSES IN PATIENTS WITH VARIOUS GENOTYPES OF CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY, Journal of lipid research, 38(6), 1997, pp. 1204-1216
High density lipoprotein (HDL) with and without apolipoprotein (apo) E
was quantified and characterized in subjects with three genotypes of
cholesteryl ester transfer protein (CETP) deficiency: the nonsense mut
ation in intron 14 (10 homozygotes and 5 heterozygotes); the missense
mutation in the exon 15 (3 homozygotes and 9 heterozygotes); and the I
nt14A/D442G in 6 compound heterozygotes. ApoE-poor and apoE-rich HDL-c
holesterol levels were elevated significantly in all genotypic groups
with the decrease in CETP activity, indicating that both types of HDL-
cholesterol can be a substrate for CETP. However, an unchanged or only
slightly increased serum apoA-II level in each genotype indicated tha
t the HDL particles with apoA-II are relatively resistant to CETP-medi
ated lipid transfer. Serum apoE-rich HDL level was considerably higher
in the Int14A homozygotes than in the compound heterozygotes, in spit
e of similar apoE-poor HDL-cholesterol levels, which may indicate that
apoE-rich HDL is a better substrate for CETP than apoE-poor HDL. Alth
ough the apoE-rich and apoE-poor HDL subclasses were similar in the ac
cumulation of cholesteryl ester and depletion of triglyceride, the acc
umulation of free cholesterol was unique to apoE-rich HDL, indicating
inhibited cholesterol esterification on this lipoprotein. Clinical lab
oratories should be aware of the discrepancy in HDL-cholesterol measur
ements that comes from the different recoveries of apoE-rich HDL using
commercial reagents. In conclusion, CETP deficiency causes considerab
le quantitative and compositional changes in HDL subclasses, reflectin
g a significant physiological role for CETP in HDL metabolism.