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
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Am Coll Cardiol. 2004 Mar 3;43(5):854-7. doi: 10.1016/j.jacc.2003.08.056.
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.
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.
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.
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.
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.
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。
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。
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。
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。
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。