Cholesteryl ester transfer protein and hyperalphalipoproteinemia in Caucasians.
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.
van der Steeg
Wim A
WA
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Hovingh
G Kees
GK
Klerkx
Anke H E M
AH
Hutten
Barbara A
BA
Nootenboom
Inge C
IC
Levels
Johannes H M
JH
van Tol
Arie
A
Dallinga-Thie
Gees M
GM
Zwinderman
Aeilko H
AH
Kastelein
John J P
JJ
Kuivenhoven
Jan Albert
JA
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*
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D012333:RNA, Messenger