Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy.
BACKGROUND
Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive.


OBJECTIVE
To investigate whether the insertion/deletion polymorphism of the ACE gene modifies blood pressure differences among subjects using diuretics, beta-blockers, calcium-channel antagonists, or ACE inhibitors.


METHODS
Data were used from the Rotterdam Study, a population-based, prospective, cohort study in the Netherlands, which started in 1990 and included 7983 subjects aged 55 years or older. Data from 3 subsequent cross-sectional investigations were used, as well. Subjects were included if they had high blood pressure during one or more examinations and/or used monotherapy with a diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor. A marginal, generalized, linear model was used to assess the association between the mean difference in systolic/diastolic blood pressure and antihypertensive classes stratified by the 3 genotypes.


RESULTS
In total, 3025 hypertensive individuals were included, and 6500 measurements of blood pressure were taken. The percentages of DD, ID, and II genotypes were 28.3%, 51.4%, and 20.3%, respectively. The mean differences in systolic blood pressure between the II and DD genotypes were 0.23 mm Hg (95% CI -5.48 to 5.94) for diuretics, -2.41 mm Hg (95% CI -6.72 to 1.90) for beta-blockers, 2.12 mm Hg (95% CI -4.64 to 8.89) for calcium-channel antagonists, and -2.01 mm Hg (95% CI -9.82 to 5.79) for ACE inhibitors.


CONCLUSIONS
The adjusted mean difference in diastolic and systolic blood pressure among diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by the ACE insertion/deletion polymorphism.
Schelleman
Hedi
H
Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, Netherlands.
Klungel
Olaf H
OH
van Duijn
Cornelia M
CM
Witteman
Jacqueline C M
JC
Hofman
Albert
A
de Boer
Anthonius
A
Stricker
Bruno H Ch
BH
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D007703:Peptidyl-Dipeptidase A