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.
Baudin
Bruno
B
Service de Biochimie A, Hôpital Saint-Antoine - 75571 Paris Cedex 12, France. bruno.baudin@sat.aphop-paris.fr
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D019808:Losartan / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D019808:Losartan