Endothelial constitutive nitric oxide synthase, angiotensin converting enzyme, angiotensin II type 1 receptor gene polymorphisms and endothelial functions in healthy individuals

T.S. Akpinar, A. Ozkok, M. Kose, R. Atas, A. Sumnu, O.K. Bakkaloglu, O. Erk, M.S. Kayacan, H. Oflaz, V.A. Akkaya, A.S. Demirel

Department of Internal Medicine, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. doktortimur@gmail.com

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• Angiology

INTRODUCTION: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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