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. [Diabetologia (2003) 46:514-519]

The C allele of T-786C polymorphism of eNOS gene is a genetic risk factor for endothelial dysfunction in Type 2 diabetic patients, especially among smokers.