Pollin Toni I, Damcott Coleen M, Shen Haiqing, Ott Sandra H, Shelton John, Horenstein Richard B, Post Wendy, McLenithan John C, Bielak Lawrence F, Peyser Patricia A, Mitchell Braxton D, Miller Michael, O'Connell Jeffrey R, Shuldiner Alan R
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Science. 2008 Dec 12;322(5908):1702-5. doi: 10.1126/science.1161524.
Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.
载脂蛋白C-III（apoC-III）可抑制甘油三酯水解，并与冠状动脉疾病有关。通过全基因组关联研究，我们发现约5%的兰卡斯特阿米什人是编码apoC-III（APOC3）的基因中无效突变（R19X）的杂合携带者，因此，他们体内apoC-III的表达量仅为非携带者的一半。与非携带者相比，突变携带者的空腹和餐后血清甘油三酯水平较低，高密度脂蛋白胆固醇水平较高，低密度脂蛋白胆固醇水平较低。通过冠状动脉钙化测量的亚临床动脉粥样硬化在携带者中比非携带者中更少见，这表明apoC-III的终身缺乏具有心脏保护作用。
