Akpinar T S, Ozkok A, Kose M, Atas R, Sumnu A, Bakkaloglu O K, Erk O, Kayacan M S, Oflaz H, Akkaya V A, Demirel A S
Department of Internal Medicine, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.
Eur Rev Med Pharmacol Sci. 2014;18(1):39-45.
Endothelial dysfunction is recognized as an early and initiating event in the pathogenesis of coronary artery disease. Gene polymorphisms of endothelial constitutive nitric oxide synthase (ecNOS), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) have been found to be associated with atherosclerosis. We aimed to investigate the possible effects of ecNOS, ACE and AT1R gene polymorphisms on endothelial functions in healthy population.
In 255 healthy subjects (male/female: 119/136 mean age 35.1±2.3 years) ecNOS, ACE and AT1R gene polymorphisms were assessed by polymerase chain reaction (PCR). Endothelium dependent (EDD, flow-mediated) and endothelium independent vasodilation (EID) were measured by high resolution brachial artery ultrasound and 0.5 mg sublingual nitroglycerine respectively.
ecNOS and ACE genes had no significant effect on EDD and EID. However, subjects with AT1RAC+CC genotypes had lower EDD compared to subjects with AT1RAA genotype in females (19.4 ± 6.6% vs 21.5 ± 7.8%, p = 0.041). EDD and EID were significantly negatively associated with age, body mass index, serum creatinine, glucose, uric acid and hemoglobin levels. When the data on age, uric acid, BMI, glucose, creatinine, and hemoglobin were split into 3 as low-1/3, mid-1/3 and high 1/3, there was significant graded decrease in EDD and EID with these parameters. In multiple regression analysis, age and presence of AT1RAC+CC genotype retained as significant independent factors predicting endothelial functions.
Gene polymorphisms of endothelial constitutive nitric oxide synthase and angiotensin converting enzyme had no effect on endothelial functions. However, the presence of angiotensin II type 1 receptor polymorhism (AT1RAC+CC genotype) seemed to adversely affect the endothelial functions as reflected by impaired endothelium dependent and independent vasodilatation in healthy individuals.
内皮功能障碍被认为是冠状动脉疾病发病机制中的早期起始事件。已发现内皮型一氧化氮合酶（ecNOS）、血管紧张素转换酶（ACE）和血管紧张素II 1型受体（AT1R）的基因多态性与动脉粥样硬化有关。我们旨在研究ecNOS、ACE和AT1R基因多态性对健康人群内皮功能的可能影响。
在255名健康受试者（男/女：119/136，平均年龄35.1±2.3岁）中，通过聚合酶链反应（PCR）评估ecNOS、ACE和AT1R基因多态性。分别通过高分辨率肱动脉超声和0.5mg舌下硝酸甘油测量内皮依赖性（EDD，血流介导的）和非内皮依赖性血管舒张（EID）。
ecNOS和ACE基因对EDD和EID无显著影响。然而，在女性中，与具有AT1R AA基因型的受试者相比，具有AT1R AC + CC基因型的受试者的EDD较低（19.4±6.6%对21.5±7.8%，p = 0.041）。EDD和EID与年龄、体重指数、血清肌酐、血糖、尿酸和血红蛋白水平显著负相关。当将年龄、尿酸、BMI、血糖、肌酐和血红蛋白的数据分为低1/3、中1/3和高1/3时，EDD和EID随这些参数显著分级降低。在多元回归分析中，年龄和AT1R AC + CC基因型的存在保留为预测内皮功能的显著独立因素。
内皮型一氧化氮合酶和血管紧张素转换酶的基因多态性对内皮功能无影响。然而，血管紧张素II 1型受体多态性（AT1R AC + CC基因型）的存在似乎对内皮功能产生不利影响，这在健康个体中表现为内皮依赖性和非内皮依赖性血管舒张受损。
