PharmGKB submission update: IX. ADRB1 gene summary.

Gene Common Name: 1 Adrenergic Receptor ( 1AR) Introductory Information: The 1-adrenergic receptor ( 1AR) is a G-protein-coupled receptor that was first characterized by its pharmacological specificity. The gene for this receptor (ADRB1) was cloned in 1987 from a placental cDNA library and subsequently mapped to chromosome 10q24-q26 (10q25.3). The intronless gene consists of 1,714 bp and codes for a 51.3 kDa protein consisting of 477 amino acid residues. 1ARs are the predominant AR subtype expressed in cardiac tissue, where they mediate the heart rate and contractility. 1AR expression in renal, vascular, and adipose tissues is also physiologically important. The A145G (Ser49Gly) and C1165G (Arg389Gly) variants are the most common and well studied in the 1AR gene. The variant at codon 49 results in increased agonist-promoted desensitization, whereas the codon 389 polymorphism alters G-protein coupling and adenylyl cyclase activity. The impact of these polymorphisms on cardiovascular disease and drug response has been the subject of numerous investigations, which were recently reviewed in detail. Three other validated SNPs are currently documented in dbSNP, two of which have been confirmed by SeattleSNPs. Several other SNPs have been reported but not validated. The functional consequences of these other polymorphisms are unknown.