GLU-27 variant of beta2-adrenergic receptor polymorphisms is an independent risk factor for coronary atherosclerotic disease.

OBJECTIVE

Arg16Gly and Gln27Glu polymorphism of beta(2)-adrenergic receptors (beta 2AR) have been associated with several risk factors for coronary atherosclerotic disease (CAD). Nevertheless, conflicting data have been reported concerning their influence on CAD and cardiovascular clinical events.

AIM

To investigate whether (a) beta 2AR polymorphisms are associated with CAD; and (b) the potential impact, if any, of these polymorphisms on cardiovascular clinical events in patients presenting with angina-like pain or silent ischemia.

METHODS AND RESULTS

We screened 786 consecutive patients referred to cardiac catheterization because of angina-like pain or silent ischemia for Arg16Gly, Gln27Glu, Thr164Ile beta 2AR polymorphisms. Patients were divided in 2 groups according to the presence or absence of CAD at the angiography. Hundred subjects from blood donor center served as controls. Clinical endpoints were evaluated at baseline and up to 6 years follow-up. Glu-27 homozygous genotype and Glu-27 allele (Glu-27, allele frequency: 47% CAD versus 39% NO CAD, p<0.05) were more frequent in patients with CAD. At multivariate analysis, patients carrying Glu-27 allele showed a significantly higher risk of developing CAD (OR: 1.78, 95% CI: 1.21-2.63, p=0.004). At clinical follow-up, a higher incidence of coronary revascularization was noted in Glu-27 homozygotes as compared with Gln-27 homozygote patients.

CONCLUSIONS

In patients at high risk for CAD and/or angina-like pain, Glu-27 allele of beta2 adrenergic receptor polymorphism is an independent risk factor for CAD and appears to be associated with higher incidence of myocardial revascularization.