Genetic Polymorphism on Type 2 Receptor of Angiotensin II, Modifies Cardiovascular Risk And Systemic Inflammation in Hypertensive Males

• Published in: American journal of hypertension 2010-03, Vol.23 (3), p.237-242
• Main Authors: Tousoulis, Dimitris, Koumallos, Nikolaos, Antoniades, Charalambos, Antonopoulos, Alexios S., Bakogiannis, Constantinos, Milliou, Antigoni, Marinou, Kyriakoula, Kallikazarou, Eleftheria, Stefanadi, Elli, Mentzikof, Dimitris, Stefanadis, Christodoulos
• Format: Article
• Language: English
• Subjects: Angiotensin; Arterial hypertension. Arterial hypotension; atherosclerosis; Biological and medical sciences; Blood and lymphatic vessels; blood pressure; Cardiology. Vascular system; cardiovascular risk; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Coronary Angiography; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - etiology; Coronary Artery Disease - genetics; European Continental Ancestry Group - genetics; genetics; Greece; Humans; hypertension; Hypertension - complications; inflammation; Inflammation - diagnostic imaging; Inflammation - etiology; Inflammation - genetics; Male; Medical sciences; Middle Aged; Polymorphism, Genetic; Receptor, Angiotensin, Type 2 - genetics; Risk
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2009.233

Background Angiotensin type 2 receptor (AT2R), plays a crucial role in blood pressure regulation and atherogenesis. AT2R gene is located on chromosome X and the biological effect of polymorphism A1675G in this gene needs to be further specified. We examined the impact of A1675G on the risk and the severity of coronary artery disease (CAD), and the expression of proatherogenic inflammatory molecules in hypertensive patients. Methods The study population consisted of 146 with CAD (102 with hypertension) and 266 age-matched individuals without CAD (114 with hypertension). The presence of A1675G polymorphism on AT2R gene was determined by PCR. Serum levels of C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in all the participants. Results The G allele was associated with decreased risk of CAD among hypertensives (odds ratio (OR) (95% confidence interval (CI))): 0.4 (0.2–0.9), P = 0.01) and less aggressive angiographic CAD (P < 0.001). The G allele was associated with lower IL-6 (median (25–75th percentile): 1.4 (0.6–3.8)), sVCAM-1 (621 (476–799)), CRP (1.2 (0.6–1.7)), and fibrinogen (369 (320–416)) vs. A allele (IL-6: 2.4 (1.1–4.5) P < 0.01, sVCAM-1: 702 (548–925) P < 0.05, CRP: 3.5 (2.0–6.1) P < 0.001, and fibrinogen: 407 (348–514) P < 0.01). The effect of A1675G on serum IL-6, sVCAM-1, and fibrinogen was driven by its effect among hypertensives (IL-6 3.1 (2.1–5.6 in A vs. 1.2 (0.3–3.4) in G P < 0.001, sVCAM-1: 890 (560–1000) in A vs. 556 (377–788) in G P < 0.01, and fibrinogen: 408 (354–510) in A vs. 369 (324–418) in G P < 0.001) whereas it had no effect among nonhypertensives. Conclusions Genetic polymorphism A1675G on AT2R gene affects cardiovascular risk and the severity of atherosclerosis by modifying systemic inflammation, especially in hypertensive males.