title: Cholesteryl ester transfer protein and hyperalphalipoproteinemia in Caucasians.
abstract: It is unclear whether cholesteryl ester transfer protein (CETP) contributes to high density lipoprotein cholesterol (HDL-C) levels in hyperalphalipoproteinemia (HALP) in Caucasians. Moreover, even less is known about the effects of hereditary CETP deficiency in non-Japanese. We studied 95 unrelated Caucasian individuals with HALP. No correlations between CETP concentration or activity and HDL-C were identified. Screening for CETP gene defects led to the identification of heterozygosity for a novel splice site mutation in one individual. Twenty-five heterozygotes for this mutation showed reduced CETP concentration (-40%) and activity (-50%) and a 35% increase of HDL-C compared with family controls. The heterozygotes presented with an isolated high HDL-C, whereas the remaining subjects exhibited a typical high HDL-C/low-triglyceride phenotype. The increase of HDL-C in the CETP-deficient heterozygotes was primarily attributable to increased high density lipoprotein containing apolipoprotein A-I and A-II (LpAI:AII) levels, contrasting with an increase in both high density lipoprotein containing apolipoprotein A-I only and LpAI:AII in the other group. This study suggests the absence of a relationship between CETP and HDL-C levels in Caucasians with HALP. The data furthermore indicate that genetic CETP deficiency is rare among Caucasians and that this disorder presents with a phenotype that is different from that of subjects with HALP who have no mutation in the CETP gene.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Wim A
authors.initials: WA
authors.lastname: van der Steeg
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.forename: Anke H E M
authors.initials: AH
authors.lastname: Klerkx
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
authors.forename: Inge C
authors.initials: IC
authors.lastname: Nootenboom
authors.forename: Johannes H M
authors.initials: JH
authors.lastname: Levels
authors.forename: Arie
authors.initials: A
authors.lastname: van Tol
authors.forename: Gees M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People / Q000235:genetics*
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D012333:RNA, Messenger