title: The beta1-adrenergic receptor mediates the pharmacogenetic interaction of the ACE D allele and beta-blockers.
abstract: 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.
authors.affiliation: Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Ishizawar
authors.forename: Karen M
authors.initials: KM
authors.lastname: Janosko
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Teuteberg
authors.forename: Linda M
authors.initials: LM
authors.lastname: Cadaret
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mathier
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
mesh_terms: 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*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D007703:Peptidyl-Dipeptidase A