Cholesteryl ester transfer protein and hyperalphalipoproteinemia in Caucasians

被引:29
作者
van der Steeg, Wim A.
Hovingh, G. Kees
Klerkx, Anke H. E. M.
Hutten, Barbara A.
Nootenboom, Inge C.
Levels, Johannes H. M.
van Tol, Arie
Dallinga-Thie, Gees M.
Zwinderman, Aeilko H.
Kastelein, John J. P.
Kuivenhoven, Jan Albert
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1105 AZ Amsterdam, Netherlands
[3] Erasmus Univ, Med Ctr, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands
关键词
deficiency; mutation; CETP-IVS7+1;
D O I
10.1194/jlr.M600405-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-H (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.
引用
收藏
页码:674 / 682
页数:9
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