Is there a role of the Thr164Ile-beta(2)-adrenoceptor polymorphism for the outcome of chronic heart failure?

ABSTRACT

OBJECTIVE: The Thr164Ile-beta(2)-adrenoceptor (AR) polymorphism exhibits lower affinities for catecholamines and reduced basal and agonist-stimulated adenylyl cyclase activity in vitro. It has been suggested that patients with chronic heart failure (CHF) due to ischemic or dilated cardiomyopathy carrying the Thr164Ile-beta(2)AR polymorphism exhibit much more rapid progression to death or heart transplantation (HTX) than CHF-patients carrying the homozygous Thr164-beta(2)AR. This study aimed to further evaluate the role of the Thr164Ile-beta(2)AR in CHF. For this we hypothesized that the Thr164Ile-beta(2)AR variant should be more abundant in HTX-patients than in patients with stable CHF or healthy controls. METHODS AND RESULTS: We genotyped 309 HTX-patients, 520 stable CHF-patients and 328 healthy controls for the three beta(2)AR variants Arg16Gly, Gln27Glu and Thr164Ile. The prevalence of the Thr164Ile-beta(2)AR variant was not considerably different in HTX-patients (2.3%) from that in CHF-patients (1.9%) or healthy controls (2.1%). Similarly, the frequency of the minor Ile164-allele was f(-)=0.0106 in HTX-patients, f(-)=0.0096 in CHF-patients and f(-)=0.0113 in healthy controls. CONCLUSIONS: The prevalence of the hypofunctional Thr164Ile-beta(2)AR variant and the frequency of the Ile164-allele were almost identical in CHF-patients, who had undergone HTX, with those in patients with stable CHF or in healthy controls. Thus, the role of the Thr164Ile-beta(2)AR in CHF remains questionable.