【佰通生物专区】PLOS Genetics：血脂代谢物早期识别心血管疾病

佰通生物

原文地址链接：PLOS Genetics：血脂代谢物早期识别心血管疾病 相关精彩新闻：佰通生物

       2014年12月26日讯 /生物谷BIOON/ --心血管疾病指的是威胁人类健康的最常见疾病，其发病率在中国居于首位。近日，一项科学研究发现一种新的循环代谢物可能有助心血管疾病的早期诊断。
       一队来自乌普萨拉大学，卡罗林斯卡研究所和科罗拉多州立大学的科学家已经确定了冠状动脉心脏疾病事件有关的新脂质衍生分子。
       相关研究已经发表在杂志PLOS Genetics上，研究审查了已随访长达10年的3600多人血样的代谢特性。新研究已确定了两个脂质代谢产物——溶血卵磷脂和鞘磷脂与冠状心脏疾病风险减少有关。
       另一个脂类代谢物即单酸甘油酯，发现与冠状动脉心脏疾病的风险增加有关。先前研究已经发现一些代谢物与冠状动脉心脏疾病相关的遗传变异有很强关联性。
       上述研究结果结果在不同的随访时间内都被复制。这项研究表明，血脂代谢产物可能对未来心血管疾病的预测有用。
       目前，研究人员正在开展体内实验调查这些代谢物对心血管疾病发展的潜在因果作用。如果得到证实，那么这些发现也可能指出新的治疗靶点。

Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease
Andrea Ganna,et al.
Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18:1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18:2 (HR = 0.81, P-value<0.001), monoglyceride 18:2 (MG 18:2; HR = 1.18, P-value = 0.011) and sphingomyelin 28:1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18:2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18:2. MG 18:2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10?7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18:2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.