Vaessen Stefan F C, Schaap Frank G, Kuivenhoven Jan-Albert, Groen Albert K, Hutten Barbara A, Boekholdt S Matthijs, Hattori Hiroaki, Sandhu Manjinder S, Bingham Sheila A, Luben Robert, Palmen Jutta A, Wareham Nicholas J, Humphries Steve E, Kastelein John J P, Talmud Philippa J, Khaw Kay-Tee
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
J Lipid Res. 2006 Sep;47(9):2064-70. doi: 10.1194/jlr.M600233-JLR200. Epub 2006 Jun 12.
In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P = 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r = 0.36 and 0.28, respectively, P < 0.001 each) but a negative correlation between apoA-V and LPL mass (r = -0.14 and -0.12 for men and women respectively, P < 0.001 each). The frequency of the c.56C>G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For -1131T>C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P = 0.047). The association of -1131T>C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V.
在小鼠模型中，载脂蛋白A-V（apoA-V）具有降低甘油三酯（TG）的作用。我们在一项巢式病例对照研究（n = 1034/2031）中，通过测定血清apoA-V水平和基因型，研究了apoA-V与TG的关系以及apoA-V与冠状动脉疾病（CAD）风险的关联。单变量和多变量分析中，apoA-V水平均与未来发生CAD无关（P值分别为0.4和0.5）。出乎意料的是，男性和女性血清apoA-V与TG之间均存在显著正相关（r值分别为0.36和0.28，P值均<0.001），但apoA-V与脂蛋白脂肪酶（LPL）质量之间呈负相关（男性和女性的r值分别为-0.14和-0.12，P值均<0.001）。尽管c.56G与apoA-V和TG水平均呈显著正相关，但c.56C>G多态性的频率在病例组和对照组之间并无差异。对于-1131T>C，次要等位基因与较低的apoA-V水平及较高的TG水平显著相关，且在病例组中过度表达（P = 0.047）。然而，-1131T>C与CAD风险的关联独立于apoA-V水平，可能是通过与载脂蛋白C3（APOC3）变体的连锁不平衡起作用。apoA-V水平与TG水平的正相关、与LPL水平的负相关以及与CAD风险缺乏关联，凸显了进一步开展人体研究以阐明apoA-V作用的必要性。
