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胆固醇与复发性事件研究中的胆固醇酯转运蛋白(CETP)TaqIB多态性:与普伐他汀治疗反应无相互作用且对心血管结局无影响:CETP TaqIB多态性对心血管结局及与降胆固醇治疗相互作用的前瞻性分析

The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome: a prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy.

作者信息

de Grooth Greetje J, Zerba Kim E, Huang Shu-Pang, Tsuchihashi Zenta, Kirchgessner Todd, Belder René, Vishnupad Priya, Hu Beihong, Klerkx Anke H E M, Zwinderman Aeilko H, Jukema J Wouter, Sacks Frank M, Kastelein John J P, Kuivenhoven Jan Albert

机构信息

Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

J Am Coll Cardiol. 2004 Mar 3;43(5):854-7. doi: 10.1016/j.jacc.2003.08.056.

Abstract

OBJECTIVES

On the basis of quantitative coronary angiography data, the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism has been postulated to predict the progression of coronary atherosclerosis and response to cholesterol-lowering therapy.

BACKGROUND

Cholesteryl ester transfer protein mediates the exchange of lipids between anti-atherogenic high-density lipoprotein (HDL) and atherogenic apolipoprotein B containing lipoproteins and therefore plays a key role in human lipid metabolism. Hence, CETP gene polymorphisms may alter susceptibility to atherosclerosis.

METHODS

To investigate the significance of the CETP TaqIB gene polymorphism with respect to clinical end points, we used the Cholesterol And Recurrent Events (CARE) cohort. The CARE study was designed to investigate the effect of five years of pravastatin therapy on coronary events.

RESULTS

We found that the odds ratios for the primary end point were not significantly different from unity for the three genetic subgroups after five years of placebo treatment. Furthermore, pravastatin induced similar changes in total cholesterol, low-density lipoprotein cholesterol, and HDL cholesterol among TaqIB genotypes, and both nonfatal myocardial infarction and deaths from coronary heart disease were reduced to the same extent in all three genotypes.

CONCLUSIONS

In the CARE cohort, the CETP TaqIB polymorphism does not predict cardiovascular events or discriminate between those who will or will not benefit from pravastatin treatment.

摘要

目的

基于定量冠状动脉造影数据,推测胆固醇酯转运蛋白(CETP)TaqIB基因多态性可预测冠状动脉粥样硬化的进展及对降胆固醇治疗的反应。

背景

胆固醇酯转运蛋白介导抗动脉粥样硬化的高密度脂蛋白(HDL)与致动脉粥样硬化的载脂蛋白B所含脂蛋白之间的脂质交换,因此在人体脂质代谢中起关键作用。因此,CETP基因多态性可能改变动脉粥样硬化的易感性。

方法

为研究CETP TaqIB基因多态性与临床终点的相关性,我们使用了胆固醇与再发事件(CARE)队列。CARE研究旨在调查普伐他汀治疗五年对冠状动脉事件的影响。

结果

我们发现,安慰剂治疗五年后,三个基因亚组的主要终点比值比与1无显著差异。此外,普伐他汀在TaqIB基因型中引起的总胆固醇、低密度脂蛋白胆固醇和HDL胆固醇变化相似,并且在所有三种基因型中,非致命性心肌梗死和冠心病死亡均降低到相同程度。

结论

在CARE队列中,CETP TaqIB多态性不能预测心血管事件,也不能区分哪些人会从普伐他汀治疗中获益或不会获益。

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