title: Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?
abstract: A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single 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 acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Podlowski
authors.forename: K
authors.initials: K
authors.lastname: Wenzel
authors.forename: H P
authors.initials: HP
authors.lastname: Luther
authors.forename: J
authors.initials: J
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Bramlage
authors.forename: G
authors.initials: G
authors.lastname: Baumann
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
authors.forename: A
authors.initials: A
authors.lastname: Speer
authors.forename: R
authors.initials: R
authors.lastname: Hetzer
authors.forename: K
authors.initials: K
authors.lastname: Köpke
authors.forename: M R
authors.initials: MR
authors.lastname: Hoehe
authors.forename: G
authors.initials: G
authors.lastname: Wallukat
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D004285:Dogs; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018342:Receptors, Adrenergic, beta-1