[Interactions between beta1 and beta2 adrenergic receptor polymorphisms as risk factors for chronic heart failure].
BACKGROUND
Beta adrenergic receptors (AR) are highly polymorphic and important regulators of cardiovascular homeostasis. Among these, beta1 and beta2 AR regulate cardiac contractility and frequency and are important pharmacological targets.


OBJECTIVE
To evaluate genotype and gene-gene interaction between beta1-AR Arg389Gly and beta2-AR Arg16Gly, Gln27Glu and Thr164Ile polymorphisms, as risk factors for HF.


METHODS
Eighty chronic HF patients and eighty-eight controls matched by age and sex were genotyped for beta1-AR Arg389Gly, beta2-AR Arg16Gly, Gln27Glu and Thr164Ile polymorphisms.


RESULTS
The presence of beta2-AR Glu allele was a risk predictor for HF (odds ratio (OR) = 2.81; 95% confidence intervals (CI) = 1.49-5.31). Interactions that increased the risk for HF were found in patients carrying at least one of the beta2-AR Glu and beta2-AR Gly allele (OR = 3.81; 95% CI = 1.50-0.70) and beta2-AR Glu and beta1-AR Gly allele combination (OR = 5.51; 95% CI = 2.19-13.86). Furthermore, the frequency of beta2-AR Glu allele was higher among patients with a history of acute myocardial infarction (with infarction: 0.534, without: 0.313, p = 0.01).


CONCLUSIONS
Beta2-AR Glu allele could be a risk predictorfor HF. This risk could be enhanced by the additional presence of beta2-AR Gly16 or beta1-AR Arg389 alleles. The frequency of beta2-AR Gln27 Glu allele was higher among patients with a history of myocardial infarction.
Moraga
Francisco
F
Unidad Farmacogenómica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
Troncoso
Rodrigo
R
Mellado
Rosemarie
R
Díaz-Araya
Guillermo
G
Vukasovic
José Luis
JL
Greig
Douglas
D
Perez
Osvaldo
O
García
Lorena
L
Roldán
Juan
J
Ocaranza
María Paz
MP
Jali
Jorge
J
Chiong
Mario
M
Castro
Pablo
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2