ADRB2 G16R - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

To be considered sufficiently evaluated a variant must have both "variant evidence" and "clinical importance" scores filled in.

Please help improve GET-Evidence by evaluating evidence for this variant!

Curation:
Currentness:

(See the latest version)

ADRB2 G16R

(ADRB2 Gly16Arg)


You are viewing an old version of this page that was saved on November 29, 2012 at 6:39am by Genome Importing Robot.

Short summary

 

Variant evidence
Computational 5

PolyPhen: Possibly damaging 0.269
SIFT: Affect protein function 0.00
GVGD: GV 0.00; GD 125.13; Class C65
Variant Effect Predictor (Ensembl ):
SIFT=deleterious(0.02);
PolyPhen=benign(0.002);
Condel=deleterious(0.942)
Mutation Tasting Prediction: Polymorphism, P value: 0. 715412 (aa 1-34 TOPO_DOM Extracellular gets lost; aa 15-15 CARBOHYD N-linked (GlcNAc…) might get lost (downstream of altered splice site)

Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr5:148206440: 41.3% (4445/10758) in EVS
  • A @ chr5:148186632: 39.1% (50/128) in GET-Evidence
  • Frequency shown in summary reports: 41.3% (4445/10758)

Publications
 

Green SA, Turki J, Innis M, Liggett SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 1994 Aug 16;33(32):9414-9. Erratum in: Biochemistry 1994 Nov 29;33(47):14368. PubMed PMID: 7915137.

 

Dishy V, Sofowora GG, Xie HG, Kim RB, Byrne DW, Stein CM, Wood AJ. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med. 2001 Oct 4;345(14):1030-5. PubMed PMID: 11586955.

 

Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ, Deykin A, Fagan JK, Fahy JV, Fish J, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF Jr, Liggett SB, Martin RJ, Mitra N, Peters SP, Silverman E, Sorkness CA, Szefler SJ, Wechsler ME, Weiss ST, Drazen JM; National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 2004 Oct 23-29;364(9444):1505-12. PubMed PMID: 15500895.

 

Pacanowski MA, Gong Y, Cooper-Dehoff RM, Schork NJ, Shriver MD, Langaee TY, Pepine CJ, Johnson JA; INVEST Investigators. beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension. Clin Pharmacol Ther. 2008 Dec;84(6):715-21. Epub 2008 Jul 9. PubMed PMID: 18615004; PubMed Central PMCID: PMC2675574.

 

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het A @ chr5:148206440

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het A @ chr5:148206440

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het A @ chr5:148206440

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het A @ chr5:148206440

 

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het A @ chr5:148206440

 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het A @ chr5:148206440

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het A @ chr5:148206440

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het A @ chr5:148206440

 

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het A @ chr5:148206440

 

 

Added in this revision:

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
hom A @ chr5:148206440

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het A @ chr5:148206440

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het A @ chr5:148206440

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het A @ chr5:148206440

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het A @ chr5:148206440

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr5:148206440

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr5:148186633

 

GS18501 - var-GS18501-1100-36-ASM
het A @ chr5:148186633

 

GS18502 - var-GS18502-1100-36-ASM
het A @ chr5:148186633

 

GS18504 - var-GS18504-1100-36-ASM
het A @ chr5:148186633

 

GS18508 - var-GS18508-1100-36-ASM
het A @ chr5:148186633

 

GS18517 - var-GS18517-1100-36-ASM
het A @ chr5:148186633

 

GS18526 - var-GS18526-1100-36-ASM
hom A @ chr5:148186633

 

GS18537 - var-GS18537-1100-36-ASM
hom A @ chr5:148186633

 

GS18555 - var-GS18555-1100-36-ASM
het A @ chr5:148186633

 

GS18558 - var-GS18558-1100-36-ASM
het A @ chr5:148186633

 

GS18947 - var-GS18947-1100-36-ASM
het A @ chr5:148186633

 

GS19017 - var-GS19017-1100-36-ASM
het A @ chr5:148186633

 

GS19025 - var-GS19025-1100-36-ASM
het A @ chr5:148186633

 

GS19129 - var-GS19129-1100-36-ASM
het A @ chr5:148186633

 

GS19239 - var-GS19239-1100-36-ASM
hom A @ chr5:148186633

 

GS19240 - var-GS19240-1100-36-ASM
het A @ chr5:148186633

 

GS19649 - var-GS19649-1100-36-ASM
hom A @ chr5:148186633

 

GS19669 - var-GS19669-1100-36-ASM
het A @ chr5:148186633

 

GS19700 - var-GS19700-1100-36-ASM
hom A @ chr5:148186633

 

GS19701 - var-GS19701-1100-36-ASM
hom A @ chr5:148186633

 

GS19703 - var-GS19703-1100-36-ASM
hom A @ chr5:148186633

 

GS19704 - var-GS19704-1100-36-ASM
hom A @ chr5:148186633

 

GS19735 - var-GS19735-1100-36-ASM
hom A @ chr5:148186633

 

GS19834 - var-GS19834-1100-36-ASM
het A @ chr5:148186633

 

GS20502 - var-GS20502-1100-36-ASM
hom A @ chr5:148186633

 

Other external references
 

    dbSNP
  • rs1042713
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Coronary Artery Disease; Death; Hypertension; Myocardial Infarction; Stroke]
    [atenolol; verapamil]
    None of the ADRB2 haplotypes tested that contained this SNP were associated with differential primary outcome (i.e., the first incidence of death, nonfatal myocardial infarction, or nonfatal stroke) in hypertensive patients with coronary artery disease.
    www.ncbi.nlm.nih.gov/pubmed/18615004
  • [Asthma]
    [salbutamol]
    Subjects who are homozygous for Arg16 and who were on regular albuterol treatment were reported to have lower morning peak flows compared with those who were not on regular albuterol treatment, suggesting that regular albuterol therapy may not be appropriate for Arg16 homozygous subjects.
    www.ncbi.nlm.nih.gov/pubmed/15500895
  • [Stress]
    [isoproterenol]
    In healthy subjects, the Arg16 variant was associated with enhanced isoproterenol-mediated desensitization of the vasculature and enhanced isoproterenol induced-venodilation, suggesting that it may be an important determinant of the vascular response to stress.
    www.ncbi.nlm.nih.gov/pubmed/11586955
  • Gly16 receptor had an enhanced agonist-promoted downregulation relative to Arg16 in in vitro studies using chinese hamster fibroblasts with expressed ADRB2.
    www.ncbi.nlm.nih.gov/pubmed/7915137
    PolyPhen-2
  • Score: 0.001 (benign)
    Web search results (161 hits -- see all)
  • JACC -- Sehnert et al. 0 (2008): j.jacc.2008.05.022v1 Table BL6
    Table 6 Results of Genetic Studies in Beta-Blocker–Treated Heart ... ADRB2 G16R. ADRB2 Q27E. ADRA2C Del322-325. ADRB1 49/389 SR, SG, GR. ADRB2 16/27 RQ, GE, GQ ...
    content.onlinejacc.org/cgi/content-nw/full/...
  • Lack of Association Between Adrenergic Receptor Genotypes and ...
    Still not a subscriber to JACC Imaging or JACC Interventions? ... ADRB2 G16R. ADRB2 Q27E. ADRA2C Del322-325. ADRB1 49/389 SR, SG, GR. ADRB2 16/27 RQ, GE, GQ ...
    content.onlinejacc.org/cgi/content/full/...
  • OIII-B-1
    G16R, Q27E, C523A. Logistic regression was performed to model. the number of drugs taken ... ADRB2 haplotype may have a significant effect on risk for heart ...
    info.medicine.ufl.edu/cardio/INVEST/...
  • GeneCanvas
    The nomenclature system used for polymorphisms is the following : Polymorphisms in the 5' ... ADRB2/G16R. ADRB2/Q27E. ADRB2/T-20C. ADRB2/T-47C (C19R of leader cistron) ...
    genecanvas.idf.inserm.fr/infusions/.../PolymorphismsList.php
  • Haplotype Analysis of the 2 Adrenergic Receptor Gene and Risk ...
    2 adrenergic receptor (ADRB2), in particular G16R, Q27E, and T164I, have ... American men, we evaluated the G16R, Q27E, and T164I polymorphisms among 523 individuals who ...
    www.genetics.org/cgi/reprint/169/3/1583.pdf
  • Haplotype Analysis of the β2 Adrenergic Receptor Gene and ...
    THE β2 adrenergic receptor (ADRB2), a member of the G-protein-coupled receptor ... of polymorphisms in ADRB2 have been identified; in particular, G16R, Q27E, and T164I ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC1449541
  • Haplotype Analysis of the {beta}2 Adrenergic Receptor Gene ...
    THE ß2 adrenergic receptor (ADRB2), a member of the G-protein-coupled receptor ... of polymorphisms in ADRB2 have been identified; in particular, G16R, Q27E, and T164I ...
    www.genetics.org/cgi/content/full/169/3/1583
  • CARDIODX™ - Publications
    CardioDx is a cardiovascular genomic diagnostics company that provides cardiologists with ... Genotypes and haplotypes of ADRB1, ADRB2, and ADRA2C did not significantly affect ...
    www.cardiodx.com/news-and-resources/publications-1
  • Influence of β2-adrenergic receptor (<i>ADRB2</i>) haplotypes ...
    Influence of 2-adrenergic receptor (ADRB2) haplotypes on obesity-related traits and ... Three polymorphisms were investigated, p.G16R (c.46G>A), p.E27Q (c. ...
    www.ashg.org/genetics/abstracts/abs06/f1715.htm
  • Lack of association between genotypes or haplotypes of ADRB2 ...
    Our objective was to investigate ADRB2 variants for association with juvenile ... of glycine to arginine at position 16 (G16R), and of glutamine to glutamic acid at ...
    www.ashg.org/genetics/ashg07s/f20130.htm

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in