Drug-gene interactions between genetic polymorphisms and antihypertensive therapy.
Genetic factors may influence the response to antihypertensive medication. A number of studies have investigated genetic polymorphisms as determinants of cardiovascular response to antihypertensive drug therapy. In most candidate gene studies, no such drug-gene interactions were found. However, there is observational evidence that hypertensive patients with the 460 W allele of the alpha-adducin gene have a lower risk of myocardial infarction and stroke when treated with diuretics compared with other antihypertensive therapies. With regard to blood pressure response, interactions were found between genetic polymorphisms for endothelial nitric oxide synthase and diuretics, the alpha-adducin gene and diuretics, the alpha-subunit of G protein and beta-adrenoceptor antagonists, and the ACE gene and angiotensin II type 1 (AT(1)) receptor antagonists. Other studies found an interaction between ACE inhibitors and the ACE insertion/deletion (I/D) polymorphism, which resulted in differences in AT(1) receptor mRNA expression, left ventricular hypertrophy and arterial stiffness between different genetic variants. Also, drug-gene interactions between calcium channel antagonists and ACE I/D polymorphism regarding arterial stiffness have been reported. Unfortunately, the quality of these studies is quite variable. Given the methodological problems, the results from the candidate gene studies are still inconclusive and further research is necessary.
Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
Hedi
H
Schelleman
Bruno H Ch
BH
Stricker
Anthonius
A
De Boer
Abraham A
AA
Kroon
Monique W M
MW
Verschuren
Cornelia M
CM
Van Duijn
Bruce M
BM
Psaty
Olaf H
OH
Klungel
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000009:adverse effects; D002986:Clinical Trials as Topic; D004232:Diuretics / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012107:Research Design
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics