Beta1- and beta2-adrenergic receptor polymorphisms affect susceptibility to idiopathic dilated cardiomyopathy.
OBJECTIVE
Beta1- and beta2-adrenergic receptors (ARs) play a pivotal role in myocardial function. We investigated whether functionally relevant polymorphisms within the genes encoding for these receptors indicate susceptibility to idiopathic dilated cardiomyopathy (DCM).


METHODS
This case-control association study involved 189 patients with DCM and 378 gender- and age-matched control subjects. All of the subjects were characterised by polymerase chain reaction-restriction fragment length polymorphism analysis in terms of Ser49Gly and Arg389Gly polymorphisms in the beta1-AR, and the 5' leader cistron Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in the beta2-AR. Genotype, allele and haplotype frequencies were analysed.


RESULTS
Univariate analysis showed that the distribution of genotype and allele frequencies of the beta1-Ser49Gly, beta1-Arg389Gly and beta2-Arg16Gly polymorphisms was significantly different between the patients and controls, and the beta1-Gly49/beta1-Arg389 haplotype was significantly more represented in the patients. Multivariate analysis showed that only the beta1-Gly49 variant (odds ratio 1.91; 95% confidence interval 1.24-2.95; P = 0.003) and beta2-Gly16Gly genotype (odds ratio 1.58; 95% confidence interval 1.10-2.26; P = 0.013) carriers were at significantly higher risk of developing DCM.


CONCLUSIONS
In our population from southern Italy, the Gly49 allele of the beta1-AR and the Gly16Gly genotype of the beta2-AR were significantly and independently associated with the DCM phenotype, thus suggesting their role in favouring susceptibility to the disease.
Forleo
Cinzia
C
Institute of Cardiology, University of Bari, Bari, Italy. cinzia.forleo@cardio.uniba.it
Sorrentino
Sandro
S
Guida
Pietro
P
Romito
Roberta
R
De Tommasi
Elisabetta
E
Iacoviello
Massimo
M
Pitzalis
Mariavittoria
M
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D002317:Cardiovascular Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D016277:Ventricular Function, Left
D002317:Cardiovascular Agents; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2