Ile164 variant of beta2-adrenoceptor does not influence outcome in heart failure but may interact with beta blocker treatment.
BACKGROUND
The Ile164 variant of the beta2-adrenoceptor has been shown to alter cardiovascular phenotypes and adversely affect survival in heart failure patients.


OBJECTIVE
We aimed to replicate this observation by genotyping a cohort of 451 heart failure patients for the Ile164 polymorphism.


METHODS
Patient outcome was recorded over a median follow-up period of 3.09 years, and genotypes were derived by multiplex amplification refractory mutation system PCR.


RESULTS
Genotypes were obtained for 443 patients, and 3.2% of these (14 patients) were heterozygous for the Ile164 SNP. Demographic data, cardiac function and neurohormonal profiles did not differ between genotype groups. Ile164 genotype did not significantly affect survival in this cohort (Thr164 homozygotes 48.9%, Ile164 heterozygous 42.9%, p=0.66), although multivariate analysis suggested that beta-blocker treatment may negatively impact survival in the heterozygote group.


CONCLUSIONS
This study suggests that the Ile164 polymorphism of the beta2-adrenoceptor does not have a major impact on outcome in individuals with heart failure, although it's potential interaction with beta-blockers requires further examination.
Littlejohn
Mathew D
MD
Department of Pathology and Carney Centre for Pharmacogenomics, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. littlem@vialactia.com
Palmer
Barry R
BR
Richards
A Mark
AM
Frampton
Chris M
CM
Pilbrow
Anna P
AP
Troughton
Richard W
RW
Cameron
Vicky A
VA
Kennedy
Martin A
MA
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2