Abstract 4898: Genetic Polymorphism on Type 2 Receptor of Angiotensin II Affects Systemic Inflammatory Process in Hypertensive Individuals
Introduction: Evidence suggests that there is a balance between angiotensin II effects on proatherogenic constitutive type 1, and antiatherogenic inducible type 2 (AT2R) receptors. The AT2R gene is located on chromosome X, and the biological effect of a newly described polymorphism (A1675G) in this gene is unclear. Aim: We examined the impact of A1675G polymorphism on AT2R, on the risk for coronary atherosclerosis, and its effect on the expression of proatherogenic inflammatory molecules.
Methods: The study population consisted of 437 males: 155 with coronary artery disease (111 with hypertension) and 282 healthy age-matched controls (121 with hypertension). The presence of A1675G polymorphism on AT2R gene (located in chromosome X) was determined by PCR. Serum levels of C-reactive protein, fibrinogen, interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in all the participants.
Results: The frequency of the A allele was similar among healthy individuals (41.8% 118/282) and CAD patients (47.7%, 74/155, p = NS). However the presence of the A allele was more frequent in hypertensives with CAD (55%, 59/107) than in hypertensives without CAD (35.8%, 43/120, p <0.01). Importantly, the A allele was associated with increased risk for CAD among hypertensive individuals (OR: 2.201[95%CI: 1.291–3.752], p = 0.004), an effect which was not seen among normotensive subjects (p = NS). Importantly, the presence of the A allele was also associated with significantly higher levels of CRP (mean[25th–95th percentile]: A:3.52[1.98 – 6.08] vs G:1.18[0.66 –1.71] mg/dL, p = 0.0001), fibrinogen (A:407[347–513] vs G:369[320 – 416] mg/dl, p = 0.001), IL-6 (A:1.55[3.63–5.40] vs G:0.99[0.51–2.46] pg/ml, p = 0.002), and sVCAM-1 (A:702[648 –925] vs G:621[476 –799] ng/ml, p = 0.03).
Conclusions: Genetic polymorphism A1675G on AT2R affects systemic inflammatory mechanisms, since the presence of the A allele is associated with higher levels of CRP, fibrinogen, IL-6 and sVCAM-1. In addition, the A allele is associated with elevated cardiovascular risk among hypertensive individuals.