apoE, a key regulator of plasma lipids, mediates altered functionalities in lipoprotein metabolism and thus affects the risk of coronary artery disease (CAD). The significance of different apoE polymorphisms remains unclear; although the ε4 allele is clearly associated with increased cholesterol levels (which inform CAD risk), direct studies about apoE polymorphisms on CAD risk and development have yielded controversial results. Furthermore, certain species of ceramides-complex lipids abundant in plasma LDL-are markers of increased risk of myocardial infarction and cardiovascular death. Using a high-throughput MS approach, we quantified 30 molecular plasma ceramide species from a cohort of 2,160 apoE-genotyped (rs7412, rs429358) young adults enrolled in the population-based Cardiovascular Risk in Young Finns Study. We then searched this lipidome data set to identify new indications of pathways influenced by apoE polymorphisms and possibly related to CAD risk. This approach revealed a previously unreported association between apoE polymorphism and a consistently documented high-risk CAD marker, Cer(d18:1/16:0). Compared with the apoE ε3/3 reference group, plasma levels of apoE ε4 were elevated and those of apoE ε2 were lowered in all subjects without evidence of apoE-by-sex interactions. apoE associated with seven ceramides that are connected to atherogenically potent macrophages and/or lipoprotein particles; these associations could indicate a plausible linkage between apoE polymorphism and ceramide metabolism, leading to adverse plasma LDL metabolism and atherogenesis. In conclusion, new evidence from plasma ceramides links apoE polymorphism with an increased risk of CAD and extends our understanding of the role of apoE in health and disease.

中文翻译：

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来自血浆神经酰胺的新证据表明，apoE 多态性与芬兰成年人患冠状动脉疾病的风险增加有关。

apoE 是血浆脂质的关键调节因子，介导脂蛋白代谢功能的改变，从而影响冠状动脉疾病 (CAD) 的风险。不同 apoE 多态性的意义仍不清楚；尽管 ε4 等位基因显然与胆固醇水平升高（可告知 CAD 风险）相关，但有关 apoE 多态性对 CAD 风险和发展的直接研究却产生了有争议的结果。此外，血浆低密度脂蛋白中富含的某些神经酰胺复合脂质是心肌梗塞和心血管死亡风险增加的标志。使用高通量 MS 方法，我们对参加基于人群的年轻芬兰人心血管风险研究的 2,160 名 apoE 基因型（rs7412、rs429358）年轻人的队列中的 30 种分子血浆神经酰胺进行了定量。然后，我们搜索了该脂质组数据集，以确定受 apoE 多态性影响且可能与 CAD 风险相关的途径的新迹象。该方法揭示了 apoE 多态性与一致记录的高风险 CAD 标记 Cer(d18:1/16:0) 之间先前未报告的关联。与apoE ε3/3参考组相比，所有受试者中apoE ε4的血浆水平升高，而apoE ε2的血浆水平降低，但没有证据表明apoE与性别之间存在相互作用。apoE 与七种神经酰胺相关，这些神经酰胺与强致动脉粥样硬化的巨噬细胞和/或脂蛋白颗粒相连；这些关联可能表明 apoE 多态性和神经酰胺代谢之间可能存在联系，从而导致不良的血浆 LDL 代谢和动脉粥样硬化形成。综上所述，