Genetic polymorphism on type 2 receptor of angiotensin II, modifies cardiovascular risk and systemic inflammation in hypertensive males.
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.
Tousoulis
Dimitris
D
1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece. tousouli@med.uoa.gr
Koumallos
Nikolaos
N
Antoniades
Charalambos
C
Antonopoulos
Alexios S
AS
Bakogiannis
Constantinos
C
Milliou
Antigoni
A
Marinou
Kyriakoula
K
Kallikazarou
Eleftheria
E
Stefanadi
Elli
E
Mentzikof
Dimitris
D
Stefanadis
Christodoulos
C
D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D006115:Greece; D006801:Humans; D006973:Hypertension / Q000150:complications*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D012306:Risk; D044465:White People / Q000235:genetics
D044139:Receptor, Angiotensin, Type 2