Abstract
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 mutation in intron 14 (10 homozygotes and 5 heterozygotes); the missense mutation in the exon 15 (3 homozygotes and 9 heterozygotes); and the Int14A/D442G in 6 compound heterozygotes. ApoE-poor and apoE-rich HDL-cholesterol 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 that the HDL particles with apoA-II are relatively resistant to CETP-mediated lipid transfer. Serum apoE-rich HDL level was considerably higher in the Int14A homozygotes than in the compound heterozygotes, in spite of similar apoE-poor HDL-cholesterol levels, which may indicate that apoE-rich HDL is a better substrate for CETP than apoE-poor HDL. Although the apoE-rich and apoE-poor HDL subclasses were similar in the accumulation of cholesteryl ester and depletion of triglyceride, the accumulation of free cholesterol was unique to apoE-rich HDL, indicating inhibited cholesterol esterification on this lipoprotein. Clinical laboratories should be aware of the discrepancy in HDL-cholesterol measurements that comes from the different recoveries of apoE-rich HDL using commercial reagents. In conclusion, CETP deficiency causes considerable quantitative and compositional changes in HDL subclasses, reflecting a significant physiological role for CETP in HDL metabolism.
Highlights
High density lipoprotein (HDL) with and without apolipoprotein E was quantified and characterized in subjects with three genotypes of cholesteryl ester transfer protein (CETP) deficiency: the nonsense mutation in intron (10 homozygotes and 5 heterozygotes); the missense mutation in the exon (3homozygotes and 9 heterozygotes); and the Int14A/D442G in 6 compound heterozygotes
Previous cases of CETP deficiency have been limited to the Japanese population, we recently found a patient, an ethnic Han Chinese, with the D442G mutation in a small scale study we carried out in China [13].Further, Funke et al [14] have reported the occurrence of hyperalphalipoproteinemia due to Abbreviations: apo, apolipoprotein;VLDL, very low density lipoproteins; LDL, low density lipoproteins; HDL, high density lipoproteins; CETP, cholesteryl ester transfer protein: Intl4A, G to A substitution at the splicing donor site of intron 14 of the cholesteryl ester transfer protein gene; D442G, aspartic acid to glycine substitution at codon 442 of the cholesteryl ester transfer protein gene; PEG, polyethylene glycol; DNA, deoxyribonucleic acid; EDTA, ethylenediamine tetraacetic acid; LCAT, lecithin: cholesterol acyltransferase
Serum total and free cholesterol, cholesteryl ester, phospholipid, apoA-I, apoC-11, apoC-111 and apoE were markedly increased in the Intl4A homozygotes and the compound heterozygotes, while little or no change was observed in the other genotypic groups
Summary
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 mutation in intron (10 homozygotes and 5 heterozygotes); the missense mutation in the exon (3homozygotes and 9 heterozygotes); and the Int14A/D442G in 6 compound heterozygotes. ApoE-poor and apoE-rich HDLcholesterol 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. Serum apoE-rich HDL level was considerably higher in the Intl4A homozygotes than in the compound heterozygotes, in spite of similar apoE-poor HDLcholesterol levels, which may indicate that apoE-rich HDL is a better substrate for CETP than apoE-poor HDL. Quantitative and compositional changes in high density lipoprotein subclasses in patients with various genotypes of cholesteryl ester transfer protein deficiency.J Lipid Res. 1997. Quantitative and compositional changes in high density lipoprotein subclasses in patients with various genotypes of cholesteryl ester transfer protein deficiency.J Lipid Res. 1997. 38: 1204-1216
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have