Angiotensin II receptor polymorphisms in hypertension. Pharmacogenomic considerations

Molecular variants of individual components of the renin-angiotensin system (RAS) are thought to contribute to inherited predisposition towards essential hypertension. Polymorphisms in genes of angiotensinogen (AGT), angiotensin I-converting enzyme (ACE) and angiotensin II type 1 receptor (AT-1) have been related to differential responses to antihypertensive drugs. AT-1 receptor mediates the major pressor and trophic actions of angiotensin II (Ang II). At least 14 AT-1 polymorphisms have been described in the gene (AGT1R); in particular the +1166 A/C polymorphism has been associated with the severe form of essential hypertension. A relationship was suggested between this polymorphism and the humoral and renal hemodynamic responses to losartan, an antihypertensive drug acting as an AT-1 blocker. Variability in the individual response to AT-1 antagonists could also be due to variations in the pharmacokinetics of the drugs. This review presents current knowledge on Ang II-receptors and polymorphisms in AGT1R related to cardiovascular disease and antihypertensive therapy.