Guangda Xiang, Linshuang Zhao, Jie Hou, Ling Yue, Huijuan Xiang
Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuluo Road 627, Wuhan 430070, Hubei Province, PR China.
Diabetes Res Clin Pract. 2006 May;72(2):155-61. doi: 10.1016/j.diabres.2005.10.004. Epub 2005 Dec 6.
Previous studies have suggested that the e4 allele of apolipoprotein E (apo E) relates to the endothelium-dependent arterial dilation in men with type 2 diabetes. This study attempted to assess whether apo e4 allele is associated with endothelial dysfunction in women with type 2 diabetes.
We selected 144 Chinese Han female type 2 diabetic patients without clinically detectable angiopathy. Polymerase chain reaction/ASO probes were used to determine their mouthwash DNA apo E genotypes, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (with increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN, an endothelium-independent dilator).
The flow-mediated arterial dilation among the subjects with e4/3 or e4/4 was 3.56+/-0.23%, which was significantly lower than that in subjects with e2/2 or e3/2 (3.97+/-0.36%) (p=0.000). The baseline vessel size, GTN-induced dilation and baseline blood flows were not significantly different among different apo E genotypes. On univariate analysis, reduced flow-mediated arterial dilation was significantly related to total cholesterol, LDL, Lp(a), high blood pressure, older age, family history of premature vascular disease, larger vessel size, duration of diabetes and e4 allele (p<0.05). By multiple stepwise regression analysis, reduced flow-mediated arterial dilation was associated with older age, large vessel size, duration of diabetes, positive family history, LDL, Lp(a) and e4 allele (p<0.01).
The apo e4 allele is associated with impairment of endothelium-dependent arterial dilation in the relatively early stage of female type 2 diabetes.
既往研究表明，载脂蛋白E（apo E）的e4等位基因与2型糖尿病男性的内皮依赖性动脉扩张有关。本研究旨在评估apo e4等位基因是否与2型糖尿病女性的内皮功能障碍相关。
我们选取了144例无临床可检测血管病变的中国汉族2型糖尿病女性患者。采用聚合酶链反应/等位基因特异性寡核苷酸探针法确定其漱口液DNA的apo E基因型，并用高分辨率超声测量静息状态下、反应性充血后（血流增加导致内皮依赖性扩张）及舌下含服硝酸甘油后（硝酸甘油，一种非内皮依赖性扩张剂）的肱动脉直径。
携带e4/3或e4/4的受试者血流介导的动脉扩张为3.56±0.23%，显著低于携带e2/2或e3/2的受试者（3.97±0.36%）（p = 0.000）。不同apo E基因型之间的基线血管大小、硝酸甘油诱导的扩张及基线血流无显著差异。单因素分析显示，血流介导的动脉扩张降低与总胆固醇、低密度脂蛋白、脂蛋白（a）、高血压、年龄较大、早发性血管疾病家族史、血管较大、糖尿病病程及e4等位基因显著相关（p < 0.05）。多因素逐步回归分析显示，血流介导的动脉扩张降低与年龄较大、血管较大、糖尿病病程、阳性家族史、低密度脂蛋白、脂蛋白（a）及e4等位基因相关（p < 0.01）。
apo e4等位基因与2型糖尿病女性相对早期的内皮依赖性动脉扩张受损有关。
