He Xin-Wei, Shen Yu-Guang, Zhu Min, Hu Xiao-Fei, Zheng Zhou, Liu Peng, Li Cai, Zhu Feng, Jin Xiao-Ping
Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China.
Public Laboratory, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China.
J Neurol Sci. 2016 Mar 15;362:333-8. doi: 10.1016/j.jns.2016.02.009. Epub 2016 Feb 4.
Angiopoietin-like protein 4 (ANGPTL4) is a central player in lipid metabolism and atherosclerosis and may thus be involved in ischaemic stroke. However, no study in humans has investigated the association of ANGPTL4 gene polymorphisms or serum levels with ischaemic stroke.
We investigated the influence of the tagged single nucleotide polymorphisms (tSNPs) rs4076317 (c.207C>G) and rs1044250 (c.797C>T; T266M) of the ANGPTL4 gene on ischaemic stroke risk in a large group of 712 large artery atherosclerotic (LAA) stroke patients and 828 controls. In addition, we examined the association of the serum ANGPTL4 levels with lipid metabolism, LAA stroke severity and ischaemic volume in a sample of 302 LAA stroke patients and 307 controls.
The findings reveal that rs4076317 exerts a co-dominant effect on lower serum TG levels compared with common homozygotes. Fewer stroke cases were homozygous for variants of rs4076317 compared with the controls (7.0% vs. 10.9%). The serum ANGPTL4 levels in patients were significantly higher than those in the controls in a univariate manner (P=0.001) and after adjustment for other risk factors (1.463 [1.215-1.835]; P<0.001). Consistently, the ANGPTL4 levels were statistically correlated with higher NIHSS scores (r=0.172, P=0.003) and larger lesion volumes (r=0.124, P=0.031).
We concluded that the tagged SNPs and high serum levels of ANGPTL4 are associated with LAA stroke and the lipid characteristics.
血管生成素样蛋白4（ANGPTL4）是脂质代谢和动脉粥样硬化的关键因子，因此可能与缺血性卒中有关。然而，尚无人体研究调查ANGPTL4基因多态性或血清水平与缺血性卒中的关联。
我们在712例大动脉粥样硬化（LAA）性卒中患者和828例对照组成的大样本中，研究ANGPTL4基因的标签单核苷酸多态性（tSNP）rs4076317（c.207C>G）和rs1044250（c.797C>T；T266M）对缺血性卒中风险的影响。此外，我们在302例LAA性卒中患者和307例对照组成的样本中，检测血清ANGPTL4水平与脂质代谢、LAA性卒中严重程度和缺血体积的关联。
研究结果显示，与常见纯合子相比，rs4076317对降低血清甘油三酯水平具有共显性作用。与对照组相比，rs4076317变异纯合子的卒中病例较少（7.0%对10.9%）。单因素分析显示患者血清ANGPTL4水平显著高于对照组（P=0.001），在调整其他危险因素后仍显著升高（1.463[1.215 - 1.835]；P<0.001）。同样，ANGPTL4水平与较高的美国国立卫生研究院卒中量表（NIHSS）评分（r=0.172，P=0.003）和较大的病灶体积（r=0.124，P=0.031）具有统计学相关性。
我们得出结论，标签SNP和高血清ANGPTL4水平与LAA性卒中和脂质特征相关。
