Blankenberg Stefan, Rupprecht Hans J, Bickel Christoph, Jiang Xian-Cheng, Poirier Odette, Lackner Karl J, Meyer Jürgen, Cambien François, Tiret Laurence
Department of Medicine II, Johannes Gutenberg-University Mainz, Mainz, Germany.
J Am Coll Cardiol. 2003 Jun 4;41(11):1983-9. doi: 10.1016/s0735-1097(03)00408-x.
We sought to evaluate the association between cholesteryl ester transfer protein (CETP) genotypes and the risk of future cardiovascular mortality in patients with coronary artery disease (CAD).
Polymorphisms of the CETP gene influence CETP activity and high-density lipoprotein (HDL) cholesterol concentration and might affect the long-term prognosis and response to statin therapy in patients with CAD.
We used serum samples and deoxyribonucleic acid collected at baseline from a prospective cohort of 1,211 patients with CAD prospectively followed up (median follow-up of 4.1 years), 82 of whom experienced a fatal cardiovascular event. The CETP/C-629A and I405V polymorphisms, CETP activity, and HDL cholesterol were determined.
Patients carrying the -629A allele had significantly lower CETP activity and higher HDL cholesterol levels. There was a significant association between this polymorphism and the risk of future cardiovascular death. Mortality decreased from 10.8% in CC homozygotes to 4.6% in CA heterozygotes and 4.0% in AA homozygotes (p < 0.0001). This association was independent of potential confounders, particularly HDL cholesterol and CETP activity levels. The clinical benefit of statin therapy was restricted to CC homozygotes, in whom cardiovascular mortality was divided by half (p = 0.01 for treatment x genotype interaction). Similar trends were observed with the CETP/I405V polymorphism, but these effects seemed to be mainly the consequence of linkage disequilibrium with the CETP/C-629A polymorphism.
In patients with CAD, the CETP/-629A allele had a strong protective effect on future mortality from cardiovascular causes, independent of its role on HDL cholesterol and CETP activity levels. Additionally, this common polymorphism appeared to predict which patients with CAD will experience a survival benefit from statin therapy.
我们旨在评估胆固醇酯转运蛋白（CETP）基因多态性与冠心病（CAD）患者未来心血管死亡风险之间的关联。
CETP基因多态性影响CETP活性和高密度脂蛋白（HDL）胆固醇浓度，并可能影响CAD患者的长期预后及对他汀类药物治疗的反应。
我们使用了来自一个前瞻性队列中1211例CAD患者基线时采集的血清样本和脱氧核糖核酸，对这些患者进行前瞻性随访（中位随访时间4.1年），其中82例发生了致命性心血管事件。测定了CETP/C - 629A和I405V多态性、CETP活性及HDL胆固醇水平。
携带 - 629A等位基因的患者CETP活性显著降低，HDL胆固醇水平较高。这种多态性与未来心血管死亡风险之间存在显著关联。死亡率从CC纯合子的10.8%降至CA杂合子的4.6%和AA纯合子的4.0%（p < 0.0001）。这种关联独立于潜在混杂因素，尤其是HDL胆固醇和CETP活性水平。他汀类药物治疗的临床益处仅限于CC纯合子，其中心血管死亡率减半（治疗×基因型交互作用p = 0.01）。在CETP/I405V多态性中观察到类似趋势，但这些效应似乎主要是与CETP/C - 629A多态性连锁不平衡的结果。
在CAD患者中，CETP/-629A等位基因对未来心血管原因导致的死亡具有强大的保护作用，独立于其对HDL胆固醇和CETP活性水平的作用。此外，这种常见的多态性似乎可以预测哪些CAD患者将从他汀类药物治疗中获得生存益处。
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