Angiotensin II type 2 receptor gene polymorphisms in cardiovascular disease

Considerable progress in our understanding of the role of the angiotensin II type 2 (AT₂) 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 AT₂ receptor agonists and antagonists suitable for human study. Nevertheless, an alternative approach involving genotyping humans for a functional polymorphism within the AT₂ receptor gene (—1332G/A) has been used in several association studies to elucidate the pathogenic role of the AT₂ 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 AT₂ receptors when compared to carriers of the A allele. Consequently, it is presently not possible to definitively interpret the role of the AT₂ receptor in human cardiovascular disease from these association studies.