Annotated PGx Gene Information for ADRB2
Submitted by: Gus Litonjua, Jaekyu Shin, Julie A. Johnson and Scott T. Weiss (PHAT and PEAR)
Reviewed by: Reviewed
Submitted date: March 22, 2006
- Jump To:
- Important Variants
- All Annotated Genes
| Gene HGNC Name: | ADRB2 |
|---|---|
| Gene Common Name: | Beta-2-AR |
| Introductory Information: | The beta-2-adrenergic receptor (Beta-2-AR) is a member of the large superfamily of G-protein-coupled receptors. The gene, ADRB2, was cloned by Kobilka in 1987 [PMID: 3025863] and localized to chromosome 5q31-q32. The gene consists of one exon (2015 nucleotides) and it encodes a 413-amino acid protein. Beta-2-AR is expressed in many cell types throughout the body and plays a pivotal role in the regulation of the cardiac, pulmonary, vascular, endocrine and central nervous system. The coding region of the gene has nine single base substitutions occurring at position 46 (Arg16Gly), 79 (Gln27Glu), 100 (Val34Met), 252, 491 (Thr164Ile), 523, 1053, 1098, and 1239. Five of these polymorphisms are degenerate and are not likely to be functionally significant, although Silverman et al. [PMID: 14610472] recently showed that SNP 523 is associated with bronchodilator responsiveness among asthmatics. Of the four non-synonymous SNPs, the two most common are Arg16Gly and Gln27Glu, and these have been widely studied. In vitro studies of agonist-stimulation have shown that the Gly16 Beta2-adrenoceptors demonstrate enhanced agonist-promoted down-regulation, while Glu27 variants seem to be resistant. Three recent meta-analyses of the two common coding polymorphisms have concluded that these polymorphisms are not associated with the diagnosis of asthma [PMID: 15867853, 15987731, 15153795]. The Gly16 allele has been associated with nocturnal asthma and with severe asthma [PMID: 15987731]. Subjects who are homozygous Arg16 and who are on regular albuterol treatment were reported to have lower morning peak flows compared with those who were not on regular albuterol treatment [PMID: 15500895]. There are two other non-synonymous coding SNPs: the Thr164Ile variant is less common (3- 5%) and the Val34Met is very rare (<1%). Within the 1.5 kb 5' untranslated region (UTR) upstream from the ATG start codon, there are eight SNPs that have been studied (-20 T/C, -47 T/C, -367 T/C, -468 C/G, -654 G/A, -1023 G/A, -1343 A/G and -1429 T/A) [PMID: 10193762]. These SNPs are in linkage disequilibrium with one another. The SNP at position -47 (Arg- 19Cys) is functionally important since it is located within a short open reading frame called the Beta Upstream Peptide (BUP) or the 5'-leader cistron. There is some evidence that this SNP affects gene expression at a translational level [PMID: 10193762]. Arg-19Cys is in linkage disequilibrium with Gln27Glu, and to a lesser extent with Arg16Gly. Among the patients prescribed beta-blocker therapy after an acute coronary syndrome, those homozygous for both Arg16 and Gln27 were at higher risk for death in 3 years (3-year mortality rate 20%) compared to the other diplotypes (3-year mortality rate 6-11%) [PMID: 16189366]. Congestive heart failure patients with Ile164 variant were at higher risk for death or heart transplantation in 1 year (event rate 76%) compared to those homozygous for Thr164 [PMID: 9788966]. |
| Key PubMed IDs: | 3025863, 15867853, 15987731, 15153795, 16189366, 9788966 |
| Key Pathways: | Beta-agonist and Beta-blocker Pathway |
| Drugs/Substrates: | Albuterol [PMID: 15500895]; beta blockers [PMID: 16189366] |
| Phenotypes/Diseases: | Asthma [PMID:15867853, 15987731, 15153795]; Acute coronary syndrome [PMID: 16189366]; Heart failure [PMID: 9788966] |
| Important Variants: | ADRB2:16Arg>Gly , ADRB2:27Glu>Gln |