Apolipoprotein e4 allele and endothelium-dependent arterial dilation in Type 2 diabetes mellitus without angiopathy

Diabetologia. 2003 Apr;46(4):514-9. doi: 10.1007/s00125-003-1060-5. Epub 2003 Mar 25.


Aims/hypothesis: Several studies have suggested a predisposing role of the e4 allele of apolipoprotein E (ApoE) in the development of atherosclerosis and cardiovascular disease in Type 2 diabetes. Therefore, we hypothesized that the e4 allele is also a risk factor for endothelial dysfunction. We attempted to assess whether Apo e4 allele is associated with endothelial dysfunction in the early stage of Type 2 diabetes.

Methods: We selected 255 Chinese Han Type 2 diabtetic men without angiopathy. PCR or allele-specific oligonucleotide probes were used to analyse ApoE genotypes, and high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia and after sublingual glyceryltrinitrate.

Results: The flow-mediated arterial dilation among the subjects with e4/3 or e4/4 was 3.14+/-0.32%, which was lower than that in subjects with e2/2 or e3/2 (4.04+/-0.30%) ( p=0.038). The baseline vessel size, glyceryltrinitrate-induced arterial dilation and baseline flow were not different among different ApoE genotypes. On univariate analysis, reduced flow-mediated arterial dilation was related to total cholesterol, LDL, lipoprotein(a) [Lp(a)], high blood pressure, older age, family history of premature vascular disease, larger vessel size, cigarette smoking, duration of diabetes and e4 allele ( p<0.05). By multiple stepwise regression analysis, reduced flow-mediated arterial dilation was associated with cigarette smoking, LDL, Lp(a), and e4 allele ( p<0.01).

Conclusion/interpretation: Apo e4 allele is associated with impairment of endothelium-dependent arterial dilation in the early stage of Type 2 diabetes.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Brachial Artery / physiology
  • China
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / physiopathology*
  • Endothelium, Vascular / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Vasodilation / genetics
  • Vasodilation / physiology*


  • Apolipoprotein E4
  • Apolipoproteins E