Annotated PGx Gene Information for ADRB1
Submitted by: Michael A. Pacanowski and Julie A. Johnson (PEAR)
Reviewed by: Scott T. Weiss (PHAT)
Submitted date: February 25, 2006
Revised: February 12, 2007
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| Gene HGNC Name: | ADRB1 |
|---|---|
| Gene Common Name: | Beta1 Adrenergic Receptor (Beta-1-AR) |
| Introductory Information: | The Beta1-adrenergic receptor (Beta-1-AR) 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) [PMID: 2825170, 2154750]. The intronless gene consists of 1,714 bp and codes for a 51.3 kDa protein consisting of 477 amino acid residues. Beta-1-ARs are the predominant Beta-AR subtype expressed in cardiac tissue, where they mediate the heart rate and contractility. Beta-1-AR expression in renal, vascular, and adipose tissues is also physiologically important. The 145 A>G (Ser49Gly) and 1165 C>G (Arg389Gly) variants are the most common and well studied in the Beta-1-AR 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 [PMID: 16120061]. Three other validated SNPs are currently documented in dbSNP, two of which have been confirmed in resequencing efforts (SeattleSNPs). Several other SNPs have been reported but not validated [PMID: 11102996, 10794544]. The functional consequences of these other polymorphisms are unknown. |
| Key PubMed IDs: | 2825170, 2154750, 11102996, 10794544, 16120061 |
| Key Pathways: | Beta-agonist and Beta-blocker Pathway, Antiarrhythmic Drug Pathways, Sympathetic Nerve Pathway |
| Drugs/Substrates: | Beta adrenergic antagonists [PMID: 12844134, 16189366, 15735607, 15864115, 15861037, 11052857, 16153393, 11787477, 12709726, 14534524, 14502278, 12921807, 16402084], Metoprolol [PMID: 12844134, 15735607, 15864115, 14534524, 12921807, 16402084], Carvedilol [PMID: 15861037], Bisoprolol [PMID: 15861037, 16325050], Atenolol [PMID:11787477, 12709726], Beta adrenergic agonists [PMID: 11753577, 16325050, 15564877], Isoproterenol, Dobutamine [PMID: 11753577, 16325050, 15564877], Epinephrine hydrochloride, Norepinephrine [PMID: 12383575, 12540530], Dopamine, Hydrochlorothiazide [PMID: 15864129, 14553962, 16109321], Xenobiotics [PMID: 11942593], Antidepressants [PMID: 12815745], Acebutolol |
| Phenotypes/Diseases: | Acquired Long QT Syndrome (aLQTS) [PMID: 11942593], Angina Pectoris [PMID: 16189366, 11704005, 16210433, 12090746], Cardiovascular Diseases [PMID: 16402084, 11787477, 12709726, 12844134, 14534524, 15864129, 14553962, 16109321, 16153393, 15735607, 15864115, 15861037, 14502278, 12921807, 16189366, 11704005, 16210433, 12090746], Heart Failure [PMID: 16153393, 15735607, 15864115, 15861037, 14502278, 12921807], Heart Failure, Congestive [PMID: 16153393, 15735607, 15864115, 15861037, 14502278, 12921807], Hypertension [PMID: 16402084, 11787477, 12709726, 12844134, 14534524, 15864129, 14553962, 16109321], Ischemia [PMID: 11704005, 16189366, 16210433, 12090746], Myocardial Ischemia [PMID: 11704005, 16189366, 16210433, 12090746], Obesity [PMID: 15685248, 15917856, 15833937, 12032746, 15833937, 15479221], Sleep Apnea, Obstructive [PMID: 16122377], Coronary Arteriosclerosis [PMID: 16189366, 11704005, 16210433, 12090746], Angina, Unstable [PMID: 16189366, 12090746], Myocardial Infarction [PMID: 16189366, 12090746], Essential hypertension [PMID: 16402084, 11787477, 12709726, 12844134, 14534524, 15864129, 14553962, 16109321], Depression [PMID: 12815745], Alzheimer Disease [PMID: 15212839] |
| Important Variants: | ADRB1:49Ser>Gly, ADRB1:389Arg>Gly |