beta(1)-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta(1)-ad renoceptor (beta(1)-AR) gene in the pathophysiology of dilated cardiomyopat hy (DCM), a severe heart disease of significant public health impact. beta( 1)-AR-mediated signal transduction is dramatically altered due to downregul ation. resulting in an impairment of myocardial response. The important rol e of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently r ecognized, we analyzed this prime candidate gene for genetic variation in c arefully selected patients and controls. In this preliminary study, 18 sing le nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino a cid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Ar g, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different b eta(1)-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mut ation in the N-terminus of the molecule in a heterozygous or homozygous for m were observed significantly more frequently in the group of IDCM patients . The present results may provide a clue on the molecular mechanisms involv ed in IDCM, and add moreover interesting information on nature, distributio n, and evolutionary aspects of sequence variation in human adrenergic recep tor genes.