Boerwinkle E, Brown S, Sharrett A R, Heiss G, Patsch W
Genetics Center, University of Texas Health Science Center, Houston 77225.
Am J Hum Genet. 1994 Feb;54(2):341-60.
To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, we have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample were similar to those reported elsewhere. Postprandial plasma retinyl palmitate response to a high-fat meal with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an epsilon 2 allele, compared with epsilon 3/3 and epsilon 3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 micrograms/dl in epsilon 2/3 individuals, compared with 1,037 micrograms/dl in epsilon 3/3 individuals and 1,108 micrograms/dl in epsilon 3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the epsilon 2/3 genotype, there is no reported evidence that the epsilon 2 allele predisposes to coronary artery disease (CAD). The results of this study provide not only a reliable estimate of the magnitude of the effect of the apo E polymorphism on various measurements commonly used to characterize postprandial lipemia, but also provide mechanistic insight into the effects of the apo E gene polymorphism on postprandial lipemia and CAD.
为了量化载脂蛋白(apo)E基因多态性对餐后血脂异常程度的影响,我们在参与双种族社区动脉粥样硬化风险研究的大量样本(N = 474)个体中,确定了其在决定对单一高脂餐反应中的作用。通过甘油三酯、富含甘油三酯的脂蛋白(TGRL)-甘油三酯、载脂蛋白B-48/载脂蛋白B-100比值和视黄醇棕榈酸酯浓度,在8小时内监测血浆中的餐后反应情况,并通过DNA扩增和酶切确定apo E基因多态性。该样本中apo E等位基因的频率及其对空腹血脂水平的影响与其他地方报道的相似。apo E基因型之间,餐后血浆视黄醇棕榈酸酯对含维生素A的高脂餐的反应存在显著差异,与ε3/3和ε3/4个体相比,携带ε2等位基因的个体清除延迟。在397名白种人样本中,ε2/3个体的平均视黄醇棕榈酸酯反应为1489微克/分升,而ε3/3个体为1037微克/分升,ε3/4个体为1108微克/分升。apo E基因多态性占餐后视黄醇棕榈酸酯反应个体间差异的7.1%,这一贡献比例大于其对空腹低密度脂蛋白胆固醇的著名影响。然而,尽管对餐后视黄醇棕榈酸酯有这种影响,但apo E基因型之间餐后甘油三酯反应情况并无显著差异。白种人样本和较小的黑人样本之间的餐后反应情况一致。虽然这些数据表明携带ε2/3基因型的个体从循环中清除残余颗粒的过程延迟,但没有报道证据表明ε2等位基因易患冠状动脉疾病(CAD)。本研究结果不仅提供了对apo E基因多态性对常用于表征餐后血脂异常的各种测量指标影响程度的可靠估计,还为apo E基因多态性对餐后血脂异常和CAD的影响提供了机制性见解。