beta1- and beta2-adrenergic receptor gene variation, beta-blocker use and risk of myocardial infarction and stroke.
BACKGROUND
The benefits of beta-blocker therapy may depend on underlying genetic susceptibility.


METHODS
We investigated the interaction of common variation in beta1 and beta2 adrenergic receptor (AR) genes with beta-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case-control study. Participants were treated pharmacologically for hypertension, aged 30-79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls.


RESULTS
We observed an interaction of beta-blocker use with beta1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other antihypertensive medications, beta-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66, 95% confidence interval (CI); 1.26-5.60) but not in homozygous carriers of the common allele (OR: 0.88, 95% CI: 0.73-1.07). Another variant, rs#2429511, interacted with beta-blocker use on both MI and ischemic stroke risks. beta-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24, 95% CI: 1.03-1.50) but not in homozygous carriers of common allele (OR: 0.70, 95% CI: 0.51-0.94). beta-blocker use did not interact with beta2-AR gene variation on the risks of MI and ischemic stroke.


CONCLUSIONS
These results, which require replication, suggest genetic variants in the beta1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease.
Lemaitre
Rozenn N
RN
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA. rozenl@u.washington.edu
Heckbert
Susan R
SR
Sotoodehnia
Nona
N
Bis
Joshua C
JC
Smith
Nicholas L
NL
Marciante
Kristin D
KD
Hindorff
Lucia A
LA
Lange
Leslie A
LA
Lumley
Thomas S
TS
Rice
Kenneth M
KM
Wiggins
Kerri L
KL
Psaty
Bruce M
BM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000517:prevention & control; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000517:prevention & control; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2