Hassan Mohamed, Wagdy Kerolos
Division of Cardiology, Aswan Heart Center, Aswan, Egypt.
Glob Cardiol Sci Pract. 2016 Jun 30;2016(2):e201614. doi: 10.21542/gcsp.2016.14.
Non-HDL cholesterol (non-HDL-C) has been introduced as an alternative cardiovascular (CV) risk marker and a secondary therapeutic target in patients with combined hyperlipidemia, diabetes mellitus, metabolic syndrome, or chronic kidney disease. An important genetic study on the Icelandic population has recently identified a strong link between a new gene - ASGR1 (for asialoglycoprotein receptor) - mutation, plasma non-HDL-C levels, and coronary heart disease (CHD). Heterozygous carriers of a rare noncoding 12-base-pair (bp) deletion (del12 deletion) in intron 4 of ASGR1 had a 13.6 mg/dl lower level of non-HDL-C and a 34% lower risk of CHD than non carriers. The cardioprotective effect of ASGR1 loss-of-function is surprisingly larger than predicted by its effect on the levels of non-HDL-C, which suggests that the atheroprotective effects of del12 mutation go beyond the lowering of serum cholesterol levels. This has shed some light on a new path - the sialylation pathway - possibly leading to a novel therapy that neutralize ASGR1 for heart disease prevention and treatment.
非高密度脂蛋白胆固醇（non-HDL-C）已被引入作为患有混合性高脂血症、糖尿病、代谢综合征或慢性肾脏病患者的替代性心血管（CV）风险标志物和次要治疗靶点。最近一项针对冰岛人群的重要基因研究发现了一个新基因——去唾液酸糖蛋白受体1（ASGR1）——的突变、血浆非高密度脂蛋白胆固醇水平与冠心病（CHD）之间的紧密联系。ASGR1第4内含子中罕见的12碱基对（bp）非编码缺失（del12缺失）的杂合携带者，其非高密度脂蛋白胆固醇水平比非携带者低13.6mg/dl，患冠心病的风险低34%。ASGR1功能丧失的心脏保护作用出人意料地大于其对非高密度脂蛋白胆固醇水平的影响所预测的结果，这表明del12突变的抗动脉粥样硬化作用超出了降低血清胆固醇水平的范围。这为一条新途径——唾液酸化途径——提供了一些线索，该途径可能会带来一种新的疗法，即通过中和ASGR1来预防和治疗心脏病。
