Angiopoietin-like protein 4 serum levels and gene polymorphisms are associated with large artery atherosclerotic stroke

J Neurol Sci. 2016 Mar 15:362:333-8. doi: 10.1016/j.jns.2016.02.009. Epub 2016 Feb 4.


Background: 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.

Methods: 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.

Results: 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).

Conclusion: We concluded that the tagged SNPs and high serum levels of ANGPTL4 are associated with LAA stroke and the lipid characteristics.

Keywords: Angiopoietin-like protein 4; Ischaemic stroke; Ischaemic volume; NIHSS scores; Single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiopoietin-Like Protein 4
  • Angiopoietins / blood*
  • Angiopoietins / genetics*
  • Atherosclerosis* / blood
  • Atherosclerosis* / complications
  • Atherosclerosis* / diagnostic imaging
  • Atherosclerosis* / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Retrospective Studies
  • Statistics, Nonparametric
  • Stroke* / blood
  • Stroke* / diagnostic imaging
  • Stroke* / etiology
  • Stroke* / genetics
  • Tomography, X-Ray Computed


  • ANGPTL4 protein, human
  • Angiopoietin-Like Protein 4
  • Angiopoietins