Agerholm-Larsen B, Nordestgaard B G, Steffensen R, Jensen G, Tybjaerg-Hansen A
Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
Circulation. 2000 Apr 25;101(16):1907-12. doi: 10.1161/01.cir.101.16.1907.
The level of HDL cholesterol is inversely related to the risk of ischemic heart disease.
In 9168 women and men from a general population and 946 women and men with ischemic heart disease (all white), we tested the hypothesis that the Ile405Val mutation in the cholesteryl ester transfer protein gene (CETP) affects HDL cholesterol levels and the risk of ischemic heart disease. The relative frequencies of Ile/Ile, Ile/Val, and Val/Val carriers were 0.46, 0.43, and 0.11 for both women and men. Women with these 3 genotypes had mean HDL cholesterol levels of 1.68, 1.75, and 1.82 mmol/L, respectively (P<0.001, ANOVA), as well as a significant decrease in the ratio of total to HDL cholesterol (P=0. 002, ANOVA). On multiple logistic regression analysis, women not treated with hormone replacement therapy who were heterozygous or homozygous for Val405 had a 1.4-fold (95% CI 1.0 to 1.9) to 2.1-fold (95% CI 1.3 to 3.4) increase in the risk of ischemic heart disease. No significant associations were found in men.
Increased HDL cholesterol levels caused by mutations in CETP are associated with an increased risk of ischemic heart disease in white women.
高密度脂蛋白胆固醇水平与缺血性心脏病风险呈负相关。
在来自普通人群的9168名女性和男性以及946名患有缺血性心脏病的女性和男性（均为白人）中，我们检验了胆固醇酯转运蛋白基因（CETP）中的Ile405Val突变影响高密度脂蛋白胆固醇水平和缺血性心脏病风险这一假设。女性和男性中Ile/Ile、Ile/Val和Val/Val携带者的相对频率分别为0.46、0.43和0.11。具有这三种基因型的女性的平均高密度脂蛋白胆固醇水平分别为1.68、1.75和1.82 mmol/L（方差分析，P<0.001），总胆固醇与高密度脂蛋白胆固醇的比值也显著降低（方差分析，P = 0.002）。在多因素逻辑回归分析中，未接受激素替代治疗且Val405杂合或纯合的女性患缺血性心脏病的风险增加了1.4倍（95%可信区间1.0至1.9）至2.1倍（95%可信区间1.3至3.4）。在男性中未发现显著关联。
CETP突变导致的高密度脂蛋白胆固醇水平升高与白人女性缺血性心脏病风险增加相关。
