β-Adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure

Although the widespread introduction of beta-adrenoceptor antagonists into the management of congestive heart failure (CHF) has led to significant improvements in morbidity and mortality, it is also apparent that clinical responses to this therapy vary substantially. With the recognition that functionally significant genetic polymorphisms of the beta(2)-adrenoceptor exist with clinically relevant allelic frequency, we hypothesized that beta(2)-adrenoceptor genotype may affect the response to carvedilol. The clinical response, influence on left ventricular function and beta(2)-adrenoceptor (beta(2)AR) genotype was determined in 80 patients treated with carvedilol. A clinically significant improvement in left ventricular function (good responder) was defined as an absolute improvement of 10% in the left ventricular ejection fraction or 5% in the fractional shortening. Consistent with studies performed in vitro on the influence of beta(2)AR genotype and receptor desensitization, subjects who were homozygous for the allele encoding the Gln(27) polymorphism displayed a significantly lower proportion of good responders than patients who were homozygous or heterozygous for the Glu(27) polymorphism (26% versus 63%, P = 0.003). These data demonstrate a significant influence of beta(2)AR genotype in the response to carvedilol in CHF patients. Accordingly, determination of beta(2)AR status may be of value in the tailoring of individual therapy in patients with CHF. (C) 2003 Lippincott Williams Wilkins.