Association Between M235T-AGT and I/D-ACE Polymorphisms and Carotid Atheromatosis in Hypertensive Patients: A Cross-Sectional Study

Abstract

Background/Aim: The renin-angiotensinaldosterone system (RAAS) may be implicated in carotid atheromatosis (CA) development. We aimed to assess the relationship of M235T-angiotensinogen (AGT) and insertion/deletion of angiotensin conversion enzyme (I/D-ACE) genotypes with CA in patients with essential hypertension (EHT). Patients and Methods: We determined the M235T-AGT and I/D-ACE genotypes, using PCR-RFLP methods, in 162 hypertensive subjects from three tertiary regional medical centers. The relationship between the studied RAAS gene polymorphisms and CA was assessed by multiple logistic regressions. Results: Hypertensive patients carrying the MT/TT235-AGT and MT235-AGT genotypes had a 2.17-fold (p=0.033) and 2.24-fold (p=0.036) increased risk to develop CA, respectively. These genotypes, MT/TT 235-AGT (OR=2.17, p=0.033) and MT235-AGT (OR=2.24, p=0.036), remain independent risk factors for CA in hypertensive patients according to the multivariate model. Conclusion: There is a statistically significant association between M235T-AGT and CA, when adjusting for several confounders and controlling for hypertension. Essential hypertension (EHT) is associated with cardiovascular risk factors, such as carotid atheromatosis (CA), dyslipidemia, obesity, left ventricular hypertrophy (LVH), and presents a high risk for ischemic coronary and cerebrovascular events (1-4). According to the World Health Organization (WHO), ischemic cardiovascular diseases are responsible for 31% of all deaths worldwide. Stroke and myocardial infarction (MI) represent 80% of all deaths of ischemic vascular cause (5). CA and the increase in carotid intima-media thickness (cIMT) in the carotid-vertebral axis are manifestations of atherosclerotic disease and diagnostic markers for ischemic heart disease (IHD) and ischemic cerebrovascular disease (6, 7). The genetic polymorphisms of the renin-angiotensinaldosterone system (RAAS) are associated with uncontrolled EHT (8, 9). RAAS influences atherosclerosis (ATS) through oxidative stress, an increase in NADPH activity, reactive oxygen species production and low-density lipoprotein cholesterol (LDL-C) peroxidation (10, 11). The components of RAAS are angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin I (AngI), angiotensin II (AngII), angiotensin II type 1 receptor (AngII R1) and angiotensin II type 2 receptor (AngII R2) (12). AGT is secreted by the liver and is converted to AngI upon the action of renin (REN). ACE converts AngI to AngII, This article is freely accessible online.

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