title: Quantitative and compositional changes in high density lipoprotein subclasses in patients with various genotypes of cholesteryl ester transfer protein deficiency.
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.
authors.affiliation: Department of Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Chiba
authors.forename: H
authors.initials: H
authors.lastname: Akita
authors.forename: K
authors.initials: K
authors.lastname: Tsuchihashi
authors.forename: S P
authors.initials: SP
authors.lastname: Hui
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Fuda
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Shibuya
authors.forename: M
authors.initials: M
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011232:Chemical Precipitation; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood* / Q000737:chemistry / Q000145:classification; D015331:Cohort Studies; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008055:Lipids; D011092:Polyethylene Glycols; D002784:Cholesterol