Important Variant 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:
- ADRB2 Overview
- All Annotated Genes
There are Two Important Variants for ADRB2.
1. ADRB2:16 Arg>Gly (rs1042713)
| Gene HGNC Name: | ADRB2 |
|---|---|
| Variant Summary: | Among Caucasians, the estimated allele frequencies are: Arg16=0.393 and Gly16=0.607. The estimated allele frequency of Arg16 among Blacks is 0.492, while among Chinese it is 0.510. Asthma and response to beta2-agonist therapy: Three recent meta-analyses have shown that the Arg16Gly polymorphism is not associated with asthma [PMID: 15867853, 15987731, and 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]. Agonist-mediated vascular response: The Arg16 allele is associated with enhanced isoproterenol- mediated vascular desensitization in healthy volunteers [PMID: 11586955]. Long-term terbutaline treatment desensitizes venous beta2-AR in a haplotype-dependent manner, with Arg16Gln27Thr164 showing greater desensitization than haplotype Gly16Gln27Thr164, which shows greater desensitization than Gly16Glu27Thr164 [PMID: 16153394]. Heart failure: The Arg16 allele is associated with higher peak oxygen consumption (peak VO2) compared to Gly16 in heart failure patients [PMID: 10785504]. However, Arg16Gly polymorphism was not associated with the improvement of left ventricular ejection fraction and decrease in heart rate to a beta blocker in stable congestive heart failure [PMID: 15861037]. In one study, the Arg16 allele was associated with lower risk of death or heart transplantation in idiopathic dilated heart failure patients [PMID: 15464701]. Acute coronary syndrome: Among the patients prescribed beta-blocker therapy after an acute coronary syndrome, patients homozygous for Arg16 had higher mortality rate (20%) vs. Gly16 carriers (10%) during 3 year follow-up period. In addition, 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]. |
| Key PubMed IDs: | 15867853, 15987731, 15153795, 11586955, 16153394, 10785504, 15861037, 15464701, 16189366 |
| Genomic Variant & GenBank ID: | 9,369,376 A>G on NT_029289 |
| mRNA Variant & GenBank ID: | 265 A>G on NM_000024 |
| Protein Variant & GenBank ID: | 16 Arg>Gly on NP_000015 |
| dbSNP rs#: | rs1042713 |
| GoldenPath Position: | chr5:148,186,633 (hg18) |
| Key Drugs/Substrates: | Albuterol [PMID: 15500895], isoproterenol [PMID: 11586955], terbutaline [PMID: 16153394], beta blockers [PMID: 16189366] |
| Key Phenotypes/Diseases: | Asthma [PMID: 15867853, 15987731, 15153795]; bronchodilator response [PMID: 10340917, 10984540]; peak expiratory flow rate [PMID: 15500895]; agonist-mediated vascular response [PMID: 11586955]; heart failure [PMID: 10785504, 15464701]; acute coronary syndrome [PMID: 16189366] |
| Phenotype Data Sets: | Both Arg16Gly and Gln27Glu have been shown to correlate with the phenotype of bronchodilator responsiveness in asthma [Phenotype file "Bronchodilator response to beta agonist in asthmatics" (PA134686740); PMID: 10984540] . |
2. ADRB2:27 Glu>Gln(rs1042714)
| Gene HGNC Name: | ADRB2 |
|---|---|
| Variant Summary: | Among Caucasians, the estimated allele frequencies are Gln27=0.754 and Glu27=0.246. The Gln27 allele is more frequent among Blacks (0.813) and among Chinese (0.910). The Glu27 allele is thought to be resistant to down regulation of the receptor [PMID: 7915137, 7598936]. Agonist-mediated vascular response: In healthy subjects, homozygous Glu27 was associated with increased isoproterenol-mediated venodilatation compared to those homozygous for Gly27 [PMID: 11586955]. Long-term terbutaline treatment desensitized venous beta2-AR in a haplotype-dependent manner, with Arg16Gln27Thr164 showing greater desensitization than haplotype Gly16Gln27Thr164, which showed greater desensitization than Gly16Glu27Thr164 [PMID: 16153394]. Heart failure: Heart failure patients homozygous for Gln27 were less likely to have improved left ventricular ejection fraction after carvedilol treatment compared to Glu27 carriers [PMID: 12835612]. However, in another study of heart failure patients, Gln27Glu polymorphism was not associated with the improvement of left ventricular ejection fraction or decrease in heart rate to a beta blocker [PMID: 15861037]. In one study, the Gln27 allele was associated with a lower risk for death or heart transplantation in idiopathic dilated heart failure [PMID:15464701]. Acute coronary syndrome: Among patients prescribed beta-blocker therapy after an acute coronary syndrome, patients homozygous for Gln27 had higher mortality rate (16%) compared to those heterozygous and homozygous for Glu27 (11% and 6%, respectively). In addition, 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]. |
| Key PubMed IDs: | 7915137, 7598936, 15867853, 15987731, 15153795, 11586955, 16153394, 12835612, 15861037, 15464701, 16189366 |
| Genomic Variant & GenBank ID: | 9,369,409 G>C on NT_029289 |
| mRNA Variant & GenBank ID: | 298 G>C on NM_000024 |
| Protein Variant & GenBank ID: | 27 Glu>Gln on NP_000015 |
| dbSNP rs#: | rs1042714 |
| GoldenPath Position: | chr5:148,186,666 (hg18) |
| Key Drugs/Substrates: | Albuterol [PMID: 15500895], isoproterenol [PMID: 11586955], terbutaline [PMID: 16153394], beta blockers [PMID: 12835612, 16189366] |
| Key Phenotypes/Diseases: | Asthma [PMID: 15867853, 15987731, 15153795]; bronchodilator response [PMID: 10984540]; agonist-mediated vascular response [PMID: 11586955]; heart failure [PMID: 15464701]; acute coronary syndrome [PMID: 16189366] |
| Phenotype Data Sets: | Both Arg16Gly and Gln27Glu have been shown to correlate with the phenotype of bronchodilator responsiveness in asthma [Phenotype file "Bronchodilator response to beta agonist in asthmatics" (PA134686740) ; PMID: 10984540]. |