The relationship between plasma angiopoietin-like protein 4 levels, angiopoietin-like protein 4 genotype, and coronary heart disease risk

Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2277-82. doi: 10.1161/ATVBAHA.110.212209. Epub 2010 Sep 9.

Abstract

Objective: To investigate the relationship between angiopoietin-like protein 4 (Angptl4) levels, coronary heart disease (CHD) biomarkers, and ANGPTL4 variants.

Methods and results: Plasma Angptl4 was quantified in 666 subjects of the Northwick Park Heart Study II using a validated ELISA. Seven ANGPTL4 single-nucleotide polymorphisms were genotyped, and CHD biomarkers were assessed in the whole cohort (N=2775). Weighted mean±SD plasma Angptl4 levels were 10.0±11.0 ng/mL. Plasma Angptl4 concentration correlated positively with age (r=0.15, P<0.001) and body fat mass (r=0.19, P=0.003) but negatively with plasma high-density lipoprotein cholesterol (r=-0.13, P=0.01). No correlation with triglycerides (TGs) was observed. T266M was independently associated with plasma Angptl4 levels (P<0.001) but was not associated with TGs or CHD risk in the meta-analysis of 5 studies (4061 cases/15 395 controls). E40K showed no independent association with plasma Angptl4 levels. In human embryonic kidney 293 and human hepatoma 7 cells compared with wild type, E40K and T266M showed significantly altered synthesis and secretion, respectively.

Conclusions: Circulating Angptl4 levels may not influence TG levels or CHD risk for the following reasons: (1) Angptl4 levels were not correlated with TGs; (2) T266M, although associated with Angptl4 levels, showed no association with plasma TGs; and (3) TG-lowering E40K did not influence Angptl4 levels. These results provide new insights into the role of Angptl4 in TG metabolism.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiopoietin-like 4 Protein
  • Angiopoietins / blood
  • Angiopoietins / genetics*
  • Biomarkers / blood
  • Cell Line
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • ANGPTL4 protein, human
  • Angiopoietin-like 4 Protein
  • Angiopoietins
  • Biomarkers