Agerholm-Larsen B, Tybjaerg-Hansen A, Schnohr P, Steffensen R, Nordestgaard B G
Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark.
Circulation. 2000 Oct 31;102(18):2197-203. doi: 10.1161/01.cir.102.18.2197.
Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl ester from HDL in exchange for triglycerides in apolipoprotein B-containing lipoproteins.
We studied 2 common mutations in CETP, A373P and R451Q, in 8467 healthy women and men from the Danish general population and in 1636 Danish women and men with ischemic heart disease. The prevalence of 373P and 451Q was 0.10 and 0.07, respectively, for heterozygous carriers and 0.003 and 0.002, respectively, for homozygous carriers. All carriers of the 451Q allele also carried the 373P allele. HDL cholesterol in female noncarriers, heterozygotes, and homozygotes of 373P was 1.74+/-0.01 (mean+/-SE), 1.62+/-0.02, and 1.38+/-0.09 mmol/L, respectively (ANOVA, P:<0.001). In men, equivalent values were 1.40+/-0.01, 1.26+/-0.02, and 1.19+/-0.09 mmol/L, respectively (ANOVA, P:<0.001). HDL cholesterol decreased similarly as a function of 451Q genotypes and all 373P/451Q genotype combinations. Furthermore, apolipoprotein AI and the HDL cholesterol/apolipoprotein AI ratio was also lower in carriers of either of these mutations for both sexes. Finally, the CETP genotype was not associated with risk of ischemic heart disease unless we adjusted for HDL cholesterol: female heterozygous and homozygous carriers versus noncarriers had 36% lower risk of ischemic heart disease (95% CI 4% to 57%); in male carriers, we observed a similar trend.
The A373P/R451Q polymorphism in CETP is associated with decreases in HDL cholesterol of 0.12 to 0.36 mmol/L in women and 0.14 to 0.21 mmol/L in men and possibly with a paradoxical 36% decrease in the risk of ischemic heart disease in women.
胆固醇酯转运蛋白（CETP）介导胆固醇酯从高密度脂蛋白（HDL）的转移，以换取含载脂蛋白B的脂蛋白中的甘油三酯。
我们研究了丹麦普通人群中8467名健康女性和男性以及1636名患有缺血性心脏病的丹麦女性和男性中CETP的2种常见突变，即A373P和R451Q。杂合子携带者中373P和451Q的患病率分别为0.10和0.07，纯合子携带者分别为0.003和0.002。所有451Q等位基因携带者也携带373P等位基因。373P的女性非携带者、杂合子和纯合子的HDL胆固醇分别为1.74±0.01（均值±标准误）、1.62±0.02和1.38±0.09 mmol/L（方差分析，P<0.001）。在男性中，相应的值分别为1.40±0.01、1.26±0.02和1.19±0.09 mmol/L（方差分析，P<0.001）。HDL胆固醇随451Q基因型以及所有373P/451Q基因型组合而有类似程度的降低。此外，载脂蛋白AI以及HDL胆固醇/载脂蛋白AI比值在这两种突变的携带者中，无论男女均较低。最后，除非我们对HDL胆固醇进行校正，否则CETP基因型与缺血性心脏病风险无关：女性杂合子和纯合子携带者与非携带者相比，缺血性心脏病风险降低36%（95%可信区间4%至57%）；在男性携带者中，我们观察到类似趋势。
CETP中的A373P/R451Q多态性与女性HDL胆固醇降低0.12至0.36 mmol/L、男性降低0.14至0.21 mmol/L有关，并且可能与女性缺血性心脏病风险出现反常的降低36%有关。
