Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia.
Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia.
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发表时间：
1998-05
影响因子：
6.5
通讯作者：
C. Bruce;D. Sharp;A. Tall
中科院分区：
文献类型：
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作者：
C. Bruce;D. Sharp;A. Tall
血浆甘油三酯（TG）水平与HDL-胆固醇水平呈负相关，高TG和低HDL胆固醇的受试者具有增加的冠心病（CHD）风险。血浆胆固醇酯转移蛋白（CETP）将胆固醇酯从HDL转移到富含TG的脂蛋白。在这项研究中，我们在檀香山心脏计划队列中的576名日本血统男性中确定了一种常见的CETP氨基酸多态性（I405 V）与CETP和HDL水平以及CHD患病率之间的关系。这种保守替换与血浆CETP浓度的改变有关（II、IV和VV基因型分别为1.95 +/- 0.54、1.91 +/- 0.57和1.77 +/- 0.57 μ g/ml）。血浆CETP浓度在VV组（而非II组）男性中的分布呈双峰（P <165 mg/dl）。虽然CHD患病率在该人群中的三种基因型之间没有显著差异，但在高血浆TG亚群中，VV受试者的CHD患病率似乎高于IV或II受试者（38% vs. 27% vs. 18%，P < 0.05，基因型和血浆TG水平的交互作用）。在一组血脂正常的受试者新鲜血浆中，V/I多态性与血浆CETP比活性的任何变化无关。数据表明，与405 V连锁不平衡的广泛和常见的CETP基因突变导致低CETP。在高胆固醇血症男性中，这与高HDL相关，并可能与CHD增加相关。
Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined the relationship between a common CETP amino acid polymorphism (I405V) and CETP and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu Heart Program cohort. This conservative substitution was associated with altered plasma CETP concentration (1.95 +/- 0.54, 1.91 +/- 0.57, and 1.77 +/- 0.57 microg/ml for the II, IV and VV genotypes, respectively). The distribution of plasma CETP concentrations among the VV, but not II, men appeared bimodal (P 165 mg/dl. Although CHD prevalence was not significantly different among the three genotypes in this population, in the subpopulation with high plasma TG, CHD prevalence appeared higher among VV than IV or II subjects (38% vs. 27% vs. 18%, P < 0.05 for an interaction of genotype and plasma TG levels). In fresh plasma from a separate group of normolipidemic subjects, the V/I polymorphism was not associated with any change in plasma CETP specific activity. The data suggest that a widespread and common CETP gene mutation(s) in linkage disequilibrium with 405V causes low CETP. Among hypertriglyceridemic men this is associated with higher HDL and possibly with increased CHD.