Angiotensin II type 2 receptor gene polymorphisms in cardiovascular disease

Abstract

Considerable progress in our understanding of the role of the angiotensin II type 2 (AT 2 ) receptor in the development of cardiac hypertrophy and coronary artery disease has been achieved using in vitro and in vivo animal models. Our understanding in humans, however, has been hindered by the lack of availability of specific AT 2 receptor agonists and antagonists suitable for human study. Nevertheless, an alternative approach involving genotyping humans for a functional polymorphism within the AT 2 receptor gene (-1332G/A) has been used in several association studies to elucidate the pathogenic role of the AT 2 receptor in cardiovascular disease. Both the A allele and the G allele have independently been associated with left ventricular remodelling. However, the methods of measuring left ventricular mass, sodium balance, age and degree of remodelling appear to influence the outcome. An association of carriers of the G allele and premature coronary artery disease has also been established, particularly in males presenting with stenotic atherosclerosis requiring revascularisation. At the molecular level, it remains unclear as to whether carriers of the G allele express more or fewer AT 2

Gene Polymorphisms of the Renin-Angiotensin-Aldosterone System as Risk Factors for the Development of In-Stent Restenosis in Patients with Stable Coronary Artery Disease

“…Consequently, it has a protective influence on cardiovascular diseases [33]. At present, regardless of the molecular basis that determines this phenomenon, and conflicting data [34], it is believed that the A allele predisposes to the development of cardiovascular pathology [35][36][37]. The results of our study are entirely consistent with this concept: hemizygotes for the A allele are significantly more frequent among men with coronary artery disease than in the control group (OR 1.833; CI 1.046-3.214).…”

Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms

“…This effect may be due to the fact that the AT2 receptor is expressed at low levels in normal tissues but upregulated in pathological states, including hypertension, vascular injury, myocardial infarction, stroke and heart failure. 23 …”

Genetic variation in angiotensin II type 2 receptor gene influences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure

“…[15][16][17] This discrepancy might be explained by the vulnerability of association studies to the effect of confounding variables that influence the eventual cardiovascular phenotype, if these are not adjusted for in statistical analyses. 18 While the effect of this +1675 G/A polymorphism on hypertrophy in patients with HCM is unknown, Deinum et al 19 reported an association between a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of AGTR2, rs11091046, and left ventricular mass index (LVMI), observed only in female HCM patients. However, this study of ungenotyped cases did not account for differences in the primary HCM causal mutation, which may have had confounding effects on the association.…”