Abstract 1629: Genetic Polymorphism A1675G On Angiotensin Receptor Type 2, Is Implicated In The Expression Of Acute Phase Proteins And The Development Of Coronary Atherosclerosis In Hypertensive Patients
Introduction: Renin-angiotensin system affects cardiovascular disease pathogenesis through a balance of angiotensin II effects on proatherogenic constitutive type 1 and antiatherogenic inducible type 2 (AT2R) receptors. The impact of A1675G polymorphism on the development of hypertension and advanced atherosclerosis is controversial. We examined the impact of A1675G polymorphism on AT2R, on the risk for arterial hypertension and coronary atherosclerosis, and its effect on the expression of proatherogenic inflammatory molecules.
Methods. The study population consisted of 310 males: 145 with arterial hypertension and 165 controls, matched for age and risk factors for atherosclerosis. Among hypertensive subjects, 37 had angiographically documented coronary atherosclerosis and 108 had no evidence of atherosclerosis. The presence of A1675G polymorphism on AT2R gene (located in chromosome X) was determined by PCR. Serum levels of C-reactive protein and fibrinogen was measured in all the participants.
Results. The frequency of the A allele was similar between patients with arterial hypertension (64/145, 44.1%) and non-hypertensive subjects (73/165, 44.2%, p=NS), while the risk for arterial hypertension was OR[95%CI]:1.004[0.641–1.574], p=0.985 for the G vs A carriers. However, the risk for coronary atherosclerosis within the group of hypertensive subjects was significantly elevated in the carriers of the A allele (OR[95%CI]:2.128[1.003–4.513], p=0.04 vs carriers of the G allele). Importantly, the presence of the A allele was also associated with significantly higher levels of CRP (4.8±0.8mg/dl) compared to the carriers of the G allele (3.0±0.3mg/dl, p<0.05). Similarly, fibrinogen levels were higher in A-allele carriers (median(25th–75th percentile) 395(340 – 455) mg/ml) compared to G-allele carriers (369(320 – 406) mg/ml, p<0.05).
Conclusions: Although genetic polymorphism A1675G on AT2R is not associated with the development of arterial hypertension, it affects the risk for coronary artery disease among hypertensive patients. The presence of the A allele also leads to higher levels of CRP and fibrinogen, implying that this polymorphism may induce atherogenesis by modulating acute phase response in hypertensive individuals.