Document Detail


Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients.
MedLine Citation:
PMID:  21395649     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: Pharmacogenetics can be used as a tool for stratified pharmacological therapy in cardiovascular medicine. We investigated whether a predefined combination of the Arg389Gly polymorphism in the adrenergic β(1) -receptor gene (ADRB1) and the Gln27Glu polymorphism in the adrenergic β(2) -receptor gene (ADRB2) could predict survival in carvedilol- and metoprolol-treated chronic heart failure (HF) patients.
METHODS: Five hundred and eighty-six HF patients (carvedilol n= 82, metoprolol n= 195) were genotyped for ADRB1 Arg389Gly (rs1801253) and ADRB2 Gln27Glu (rs1042714). The end-point was all-cause mortality, and median follow-up time was 6.7 years. Patients were classified into two functional genotype groups: group 1 combination of Arg389-homozygous and Gln27-carrier (46%) and group 2 any other genotype combination (54%). Results were fitted in two multivariate Cox models.
RESULTS: There was a significant interaction between functional genotype group and carvedilol treatment (adjusted(1) P= 0.033, adjusted(2) P= 0.040). Patients treated with carvedilol had shorter survival in functional genotype group 1 (P= 0.004; adjusted(1) hazard ratio (HR) 2.67, 95% CI 1.27, 5.59, P= 0.010; adjusted(2) HR 2.05, 95% CI 1.06, 3.95, P= 0.033). There was no interaction between genotype group and metoprolol treatment (P= 0.61), and there was no difference in overall survival between genotype groups (P= 0.69).
CONCLUSIONS: A combination of ADRB1 Arg389-homozygous and ADRB2 Gln27-carrier in HF patients treated with carvedilol was associated with a two-fold increase in mortality relative to all other genotype combinations. There was no difference in survival in metoprolol-treated HF patients between genotype groups. Patients in genotype group 1 may benefit more from metoprolol than carvedilol treatment.
Authors:
Morten Petersen; Jon T Andersen; Brian R Hjelvang; Kasper Broedbaek; Shoaib Afzal; Mette Nyegaard; Anders D Børglum; Steen Stender; Lars Køber; Christian Torp-Pedersen; Henrik E Poulsen
Related Documents :
20447629 - Microsurgical and nonmagnified subinguinal varicocelectomy for infertile men: a compara...
21453919 - The effectiveness of protocol drive, nurse-initiated discharge in a 23-h post surgical ...
21277059 - Risk factors affecting postoperative hemorrhage after tooth extraction in patients rece...
21212649 - Predictive factors of successful varicocelectomy in infertile patients.
21328679 - Safety and efficacy of drug eluting stents compared with bare metal stents for saphenou...
21359409 - D-dimer and residual vein obstruction as risk factors for recurrence during and after a...
16646649 - Bipolar transurethral resection of prostate in saline: preliminary report on clinical e...
23936029 - Neurocognitive impairment in patients treated with protease inhibitor monotherapy or tr...
24678789 - Learning curve for breast mass excision using a vacuum-assisted biopsy system.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  71     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-06-21     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  556-65     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. mortenpetersen@rh.dk
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Carbazoles / therapeutic use*
Female
Genotype
Heart Failure / drug therapy*,  genetics,  mortality
Humans
Male
Metoprolol / therapeutic use*
Middle Aged
Pharmacogenetics
Polymorphism, Genetic / genetics
Propanolamines / therapeutic use*
Proportional Hazards Models
Receptors, Adrenergic, beta / genetics*
Survival Analysis
Chemical
Reg. No./Substance:
0/Carbazoles; 0/Propanolamines; 0/Receptors, Adrenergic, beta; 0K47UL67F2/carvedilol; 37350-58-6/Metoprolol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effects of CYP2C9*1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam.
Next Document:  Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance thera...