Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits.
Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits.
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DOI：
10.1161/atvbaha.113.302802
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发表时间：
2014-05
期刊：
影响因子：
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通讯作者：
Rader DJ
中科院分区：
文献类型：
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作者：
Mehta N;Qamar A;Qu L;Qasim AN;Mehta NN;Reilly MP;Rader DJ
ANGPTL 3和ANGPTL 4是在体外抑制脂蛋白脂酶（LPL）的分泌蛋白。ANGPTL 3和ANGPTL 4基因座的遗传变异与血脂性状显著相关。本研究的目的是在一个大的社区样本中评估血浆血管生成素样蛋白3（ANGPTL 3）和4（ANGPTL 4）浓度与脂质和代谢特征的相关性。使用经验证的ELISA测定法在1770名受试者中测量血浆ANGPTL 3和ANGPTL 4水平。进行了Pearson未调整相关分析和调整年龄、性别和种族的线性回归分析。ANGPTL 3水平与低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平显著正相关（均P < 2 ×10−5），但与甘油三酯无关。相比之下，ANGPTL 4水平与LDL-C和HDL-C呈显著负相关（均P < 2 × 10−5），与甘油三酯呈正相关（P=0.003）。此外，ANGPTL 4而非ANGPTL 3水平与空腹血糖和代谢综合征显著正相关。尽管在体外具有相似的生化作用，但血浆ANGPTL 3和ANGPTL 4浓度与血浆脂质具有几乎相反的关系。ANGPTL 4与LDL-C和HDL-C呈强负相关，与代谢综合征的多种特征（包括甘油三酯）呈正相关，而ANGPTL 3与LDL-C和HDL-C呈正相关，与代谢综合征特征（包括甘油三酯）无关。虽然ANGPTL 3和ANGPTL 4都在体外抑制LPL并在体内影响脂蛋白代谢，但这些相关蛋白质的生理学及其对脂蛋白的影响明显不同且复杂。
ANGPTL3 and ANGPTL4 are secreted proteins that inhibit lipoprotein lipase (LPL) in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) concentrations with lipid and metabolic traits in a large community-based sample. Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, gender and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels (both P < 2 ×10−5) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with LDL-C and HDL-C (both P < 2 × 10−5) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome. Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with LDL-C and HDL-C and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with LDL-C and HDL-C and not with metabolic syndrome traits including triglycerides. While ANGPTL3 and ANGPTL4 both inhibit LPL in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.