Demirel S, Akkaya V, Cine N, Oflaz H, Yekeler E, Ozturk S, Cleophas T J, Fici F
Neth Heart J. 2005 Apr;13(4):126-131.
Both in animal models and humans an association between endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and the development of hypertension has been found. However, the relation between ecNOS polymorphism and endothelial function in patients with hypertension has not been systematically studied. Genes of the renin-angiotensin system include the angiotensin-converting enzyme (ACE) gene, and the angiotensin II type 1 receptor (ATIR) gene, and have been associated with essential hypertension. However, no consistent data are available about the relation between polymorphisms of these genes and the presence of endothelial dysfunction in such patients.
To assess the presence of genetic polymorphisms and of endothelial dysfunction in patients with essential hypertension. To determine the effects of gene polymorphisms on endothelial dysfunction in these subjects.
In 129 patients with essential hypertension and the same number of age-matched controls polymorphisms of the ecNOS gene, ACE gene, and AT1R gene were analysed by polymerase chain reactions. Endothelial function was assessed by maximal endothelial dependent vasodilation in response to reactive hyperaemia using high resolution ultrasound examinations of the brachial arteries. To assess correlation between genetic markers, endothelial function, and the presence of hypertension both univariate and multivariate analyses were used including Pearson's and Spearman's correlation coefficients, and multiple logistic regressions.
The size of endothelium-dependent vasodilation between patients and controls differed by 16% (p<0.02). However, the presence of genetic polymorphisms of the ecNOS, ACE, and AT1R genes did not significantly differ between patients and controls. Neither were there any statistically significant differences in endothelial function between various genotypes of the three genes. This was so for both the patients and the controls, although in all of these comparisons the controls overall displayed a slightly better endothelial function than the patients did. Multiple regression analysis with endothelial dysfunction as dependent and the presence of gene polymorphisms as independent variables did not reveal any significant correlation either.
A significant relation between endothelial dysfunction and essential hypertension was demonstrated. However, no relations between genetic markers and the presence of essential hypertension or between endothelial dysfunction and genetic markers were established. The failure of our study to demonstrate the latter may be due to confounders. Also, other genes may be more important in the pathogenesis of endothelial dysfunction and essential hypertension. The current study underscores that endothelial dysfunction and hypertension are not simple genetic disorders, and that they are, essentially, multicausal.
在动物模型和人类中，均已发现内皮型一氧化氮合酶（ecNOS）基因多态性与高血压的发生之间存在关联。然而，ecNOS基因多态性与高血压患者内皮功能之间的关系尚未得到系统研究。肾素 - 血管紧张素系统的基因包括血管紧张素转换酶（ACE）基因和血管紧张素II 1型受体（AT1R）基因，它们与原发性高血压有关。然而，关于这些基因的多态性与此类患者内皮功能障碍之间的关系，尚无一致的数据。
评估原发性高血压患者的基因多态性和内皮功能障碍情况。确定基因多态性对这些受试者内皮功能障碍的影响。
对129例原发性高血压患者和相同数量的年龄匹配对照者，采用聚合酶链反应分析ecNOS基因、ACE基因和AT1R基因的多态性。使用高分辨率超声检查肱动脉，通过反应性充血后最大内皮依赖性血管舒张来评估内皮功能。为了评估基因标志物、内皮功能和高血压存在之间的相关性，采用了单变量和多变量分析，包括Pearson和Spearman相关系数以及多元逻辑回归。
患者和对照者之间内皮依赖性血管舒张的幅度相差16%（p<0.02）。然而，患者和对照者之间ecNOS、ACE和AT1R基因的基因多态性存在情况没有显著差异。这三个基因的不同基因型之间在内皮功能方面也没有任何统计学上的显著差异。患者和对照者都是如此，尽管在所有这些比较中，对照者总体上显示出比患者略好的内皮功能。以内皮功能障碍为因变量、基因多态性存在为自变量的多元回归分析也未显示出任何显著相关性。
证实了内皮功能障碍与原发性高血压之间存在显著关系。然而，未确立基因标志物与原发性高血压存在之间的关系，也未确立内皮功能障碍与基因标志物之间的关系。我们的研究未能证实后者可能是由于混杂因素。此外，其他基因可能在内皮功能障碍和原发性高血压的发病机制中更为重要。当前研究强调内皮功能障碍和高血压并非简单的遗传疾病，本质上是多因素的。
