Role of beta1- and alpha2c-adrenergic receptor polymorphisms and their combination in heart failure: a case-control study.
BACKGROUND
Adrenergic activation has a central role in the development of HF. The function of the beta1- and the alpha2C-adrenergic receptors is influenced by gene polymorphisms: the beta1Arg389 variant is associated with increased beta1-receptor sensitivity and the alpha2C-receptor Del322-325 variant is associated with decreased alpha2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure.


METHODS
The role of the beta1- and alpha2C-adrenergic receptor gene polymorphisms as risk factors for heart failure (HF) was assessed in an Italian white Caucasian population using a case-control study design. Genomic DNA was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP).


RESULTS
We compared 260 Caucasian patients with HF and 230 normal subjects. The beta1Arg389 allele was frequent both in the patients with HF (69%) and in the normal subjects (73%). The alpha2CDel322-325 variant was rare in both groups (9% and 8%, respectively). Patients homozygotes for either the beta1Arg389 or the alpha(2C)Del322-325 alleles had no increased risk of HF (odds ratio [OR], 0.8; 95%CI: 0.5-1.2 and OR, 0.8; 95% CI: 0.4-1.8, respectively). Patients homozygotes for both the beta1Arg389 and the alpha(2C)Del322-325 alleles had no increased risk of HF as well (OR: 0.6; 95% CI: 0.2-2.1).


CONCLUSIONS
Beta1-ARs and alpha2C-ARs polymorphisms are not associated with an increased risk of HF in an Italian white Caucasian population.
Metra
Marco
M
Institute of Cardiology, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy. metramarco@libero.it
Zani
Claudia
C
Covolo
Loredana
L
Nodari
Savina
S
Pezzali
Natalia
N
Gelatti
Umberto
U
Donato
Francesco
F
Nardi
Giuseppe
G
Dei Cas
Livio
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D044465:White People / Q000235:genetics
D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1; D004247:DNA