Interactions between five candidate genes and antihypertensive drug therapy on blood pressure.
Despite the availability of effective antihypertensive drugs, there is a large variation in response to these drugs. This study investigates whether polymorphisms in the angiotensin converting enzyme (I/D), angiotensinogen (M235T), alpha-adducin (G460W), angiotensin II type 1 receptor (1166A/C), or G protein beta(3)-subunit (825C/T) gene modify the mean difference in blood pressure levels among diuretics, beta-blockers, or ACE-inhibitors users. Data were used from the Doetinchem Cohort Study, and blood pressure data were collected from GPs (1987-1997). A marginal generalized linear model (GEE) was used to assess the gene-drug interaction on the mean difference in systolic/diastolic blood pressure. In total, 625 hypertensive individuals were included with a total of 5262 measurements of blood pressure. Only the interaction between diuretic use and the GNB3 825C/T polymorphism was significant (C allele versus TT systolic blood pressure (SBP): 4.33 mmHg [95% CI: 0.14-8.54]). Thus, the mean SBP level among diuretic users may be modified by the GNB3 825C/T polymorphism.
Schelleman
H
H
Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
Stricker
B H Ch
BH
Verschuren
W M M
WM
de Boer
A
A
Kroon
A A
AA
de Leeuw
P W
PW
Kromhout
D
D
Klungel
O H
OH
D000808:Angiotensinogen / Q000235:genetics; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D000099291:Adducins
D000808:Angiotensinogen; D000959:Antihypertensive Agents; D002148:Calmodulin-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D007703:Peptidyl-Dipeptidase A; D044140:Receptor, Angiotensin, Type 1; D000099291:Adducins; C454420:G-protein beta3 subunit