女性2型糖尿病患者载脂蛋白e4等位基因与内皮依赖性血管舒张功能降低有关

Apolipoprotein e4 allele is associated with the decrease of endothelium-dependent arterial dilation in female patients with type 2 diabetes mellitus

目的 探讨女性 2型糖尿病患者载脂蛋白e(Apoe)基因型与内皮依赖性动脉舒张功能的关系。方法 选择 101例无血管并发症女性 2型糖尿病患者和 95例年龄匹配的女性健康个体,采用PCR/ASO探针杂交技术检测其Apoe基因型,同时采用高分辨血管外超声法检测肱动脉血流介导的内皮依赖性血管舒张功能和硝酸甘油(GNT)介导的内皮非依赖性血管舒张功能。结果 (1)不论在女性 2型糖尿病患者还是在对照组,e4 /3、e4 /4基因型携带者内皮依赖性血管舒张功能〔分别为(3. 22±0. 29)%和(3. 78±0. 4)%〕,均低于此 2组的e2 /2、e3 /2携带者〔分别为(3. 96±0. 33)%和(4. 74±0. 41)%,P<0. 05〕。在各基因型间,基础血管内径、基础血流和GNT介导的血管舒张差异无统计学意义。(2)多元逐步回归分析结果显示,在女性 2型糖尿病患者中,年龄、血管内径、低密度脂蛋白胆固醇 (LDL C)、脂蛋白 (a)〔Lp(a)〕、Apoe4、空腹血糖、餐后 2h血糖、HbA1c、病程及阳性心血管病家族史与血流介导的内皮依赖性血管舒张功能均呈负相关(均P<0. 01);在对照组中,血流介导的内皮依赖性血管舒张功能与年龄、血管内径、LDL C、Lp(a)、Apoe4呈负相关(均P<0. 05)。结论 在无血管并发症女性 2型糖尿病患者和健康女性中。

Objective To investigate the relationship between apolipoprotein (Apo) e4 allele and endothelium dependent arterial dilation in females with type 2 diabetes mellitus. Methods One hundred and one female type 2 diabetic patients without angiopathy, aged 40 71 years, and 95 healthy female individuals were selected. PCR/allele specific oligonucleotide probes were used to determine Apo e genotypes, and high resolution ultrasound was applied to measure brachial artery flow mediated endothelium dependent dilation and glyceryltrinitrate (GNT) mediated endothelium independent dilation. Results (1) In both diabetic patients and healthy individuals, the flow mediated endothelium dependent arterial dilation in subjects with e4/3 or e4/4 genotypes was (3.22±0.29)% and (3.78±0.34)% respectively, which were significantly lower than those in subjects with e2/2 or e3/2 genotypes 〔(3.96±0.33)% and (4.74±0.41)%, P<0.05〕. There were no significant differences in baseline vessel size, baseline flow and GNT mediated endothelium independent dilation among various genotypes. (2) By multiple stepwise regression analysis, reduced flow mediated endothelium dependent arterial dilation was associated with age, baseline vessel size, low density lipoprotein cholesterol (LDL C), Lipoprotein (a) 〔Lp(a)〕, Apo e4,fasting plasma glucose, postprandial 2h plasma glucose, HbA 1c , duration of diabetes as well as positive family history of cardiovasculardiseasesinfemaletype 2 diabetic patients (all P<0.01). Besides, reduced flow mediated endothelium dependent arterial dilation was also associated with age, baseline vessel size, LDL C, Lp(a), Apo e4 in healthy women (all P<0.05). Conclusions Apo e4 allele is associated with impairment of endothelium dependent arterial dilation in female patients with type 2 diabetes mellitus without angiopathy and in healthy women.