Mutations that inactivate the gene angiopoietin-like 3 (ANGPTL3) linked to lower risk of coronary artery disease (CAD). The study provided 3 lines of evidence: 3 individuals with complete ANGPTL3 deficiency showed 0% of coronary atherosclerotic plaque, compared with a mean of 39% in the matched control; ANGPTL3 gene sequencing (in up to 21,980 people with CAD and 158,200 control subjects) demonstrated that approximately 1 in 309 people was a heterozygous carrier for a loss-of-function (LOF) mutation. Compared with those without mutation, heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17% reduction in circulating triglycerides and a 12% reduction in low-density lipoprotein cholesterol. Carrier status was associated with a 34% reduction in risk of CAD (odds ratio: 0.66); Individuals in the lowest tertile of circulating ANGPTL3 concentrations (measured in 1,493 people who presented with MI and 3,232 control subjects), compared with the highest, had reduced risk of MI (adjusted odds ratio: 0.65). The findings suggest that ANGPTL3 is causally related to CAD. Sources: http://www.onlinejacc.org/
使类血管生成素3基因失活的突变与冠心病风险降低相关。该研究提供了3条证据：3例类血管生成素3完全缺失者显示0％冠脉粥样硬化斑块，而匹配对照者为39％; 类血管生成素3基因测序（高达21, 980例冠心病人和158,200名对照）显示大约309人中有1人是失功能突变杂合体的携带者。与无突变者相比，类血管生成素3 失功能突变杂合体的携带者循环甘油三酯降低17％，低密度脂蛋白胆固醇降低12％。携带者冠心病风险降低34％（风险比：0.66）；类血管生成素3浓度（测量了1,493例心梗患者和3,232名对照）最低三分位数与最高三分位数的个体相比，心梗风险降低了（校正的风险比：0.65）。研究结果提示类血管生成素3与冠心病有因果关系。来源：http://www.onlinejacc.org/