The beta1-adrenergic receptor mediates the pharmacogenetic interaction of the ACE D allele and beta-blockers.
The role of beta-receptor selectivity for the interaction between the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and beta-blocker therapy was investigated in 479 subjects with left ventricular dysfunction. Subjects were separated into no beta-blocker, beta1 -selective, and nonselective beta-blocker treatment groups. The D allele adversely affected transplant-free survival for subjects not on beta-blockers (p= 0.004). Treatment with selective beta1-blockers eliminated the impact of the D allele (p= 0.51) in a manner similar to nonselective beta1,2-blockers (p= 0.80). Treatment with beta1-blockers was sufficient to eliminate the adverse impact of the ACE D allele, suggesting this pharmacogenetic interaction is mediated through the beta1-receptor.
Ishizawar
David C
DC
Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Janosko
Karen M
KM
Teuteberg
Jeffrey J
JJ
Cadaret
Linda M
LM
Mathier
Michael A
MA
McNamara
Dennis M
DM
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000145:classification / Q000494:pharmacology*; D000483:Alleles; D015331:Cohort Studies; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010597:Pharmacogenetics; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D007703:Peptidyl-Dipeptidase A