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rs1801253

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(C;C) 1.1 responds well to bucindolol; may also depend on rs1801252
(C;G)
(G;G) 0
ReferenceGRCh38 38.1/141
Chromosome10
Position114045297
GeneADRB1
is asnp
is mentioned by
dbSNPrs1801253
ebirs1801253
HLIrs1801253
Exacrs1801253
Varsomers1801253
Maprs1801253
PheGenIrs1801253
hapmaprs1801253
1000 genomesrs1801253
hgdprs1801253
ensemblrs1801253
gopubmedrs1801253
geneviewrs1801253
scholarrs1801253
googlers1801253
pharmgkbrs1801253
gwascentralrs1801253
openSNPrs1801253
23andMers1801253
23andMe allrs1801253
SNP Nexus

SNPshotrs1801253
SNPdbers1801253
MSV3drs1801253
GWAS Ctlgrs1801253
GMAF0.2975
Max Magnitude1.1
? (C;C) (C;G) (G;G) 28

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine.

One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized for patients with the corresponding genotypes as follows [PMID 12844134]:

This SNP may also determine whether the drug bucindolol will have any effect on a particular patient.

In a separate study of 600+ women initially referred for coronary angiography and then followed for 6 years, during which time 115 experienced a heart problem, rs1801253(G;G) individuals were calculated to be at higher risk (adjusted hazard ratio 3.63, CI: 1.17–11.28). This risk was specifically for myocardial infarction, and was only seen in women without obstructive coronary artery disease.[PMID 18331634OA-icon.png]

Other press releases or articles include:

  • Alters response to heart failure drugs bisoprolol, metoprolol, and carvedilol [1]
  • Patent filings, such as USPTO application 20060177838 and others, include claims that "being homozygous in the .beta..sub.1AR gene to encode an arginine at position 389 {ie rs1801253} in the gene product provides the patient with a physiology that is amenable to treatment with bucindolol."
OMIM109630
DescBETA-1-ADRENERGIC RECEPTOR POLYMORPHISM, GAIN-OF-FUNCTION
Variant0001
Relatedalso


[PMID 19553224] Trp64Arg polymorphism in ADRB3 gene is associated with elite endurance performance. (This is a SNP in a different gene.)


[PMID 19743955] Polymorphisms of the beta1-adrenergic receptor gene are associated with essential hypertension in Chinese





[PMID 21444836OA-icon.png] Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension in 86 588 Individuals


ClinVar
Risk rs1801253(C;C)
Alt rs1801253(C;C)
Reference rs1801253(G;G)
Significance Drug-response
Disease Congestive heart failure and beta-blocker response
Variation info
Gene ADRB1
CLNDBN Congestive heart failure and beta-blocker response, modifier of
Reversed 0
HGVS NC_000010.10:g.115805056G>C
CLNSRC OMIM Allelic Variant
CLNACC RCV000019322.2,



[PMID 16120061OA-icon.png] The functional significance of genetic variation within the beta-adrenoceptor.


[PMID 17150099OA-icon.png] Beta2-adrenergic receptor and UCP3 variants modulate the relationship between age and type 2 diabetes mellitus.


[PMID 17335470] Studies of associations between the Arg389Gly polymorphism of the beta1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects.


[PMID 17512307OA-icon.png] Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.


[PMID 18059082] Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity.


[PMID 18187665OA-icon.png] Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease.


[PMID 18534365OA-icon.png] Common beta-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease.


[PMID 19379518OA-icon.png] Development of a fingerprinting panel using medically relevant polymorphisms.


[PMID 19842931OA-icon.png] GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans.


[PMID 20401335OA-icon.png] Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype.


[PMID 20565774OA-icon.png] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.


[PMID 20676228OA-icon.png] Lone AF - etiologic factors and genetic insights into pathophysiolgy.


[PMID 21172166OA-icon.png] Pharmacogenetics of antidepressant response.


[PMID 21395649OA-icon.png] Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients.


GET Evidence
ADRB1-G389R
aa_change Gly389Arg
aa_change_short G389R
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.680577
summary Better outcome from treatment with atenolol vs. verapamil.



Beta-Blocker Response

GWAS snp
PMID [PMID 23202124OA-icon.png]
Trait Birth weight
Title New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
Risk Allele G
P-val 4E-9
Odds Ratio .04 [0.027-0.055] gram decrease


[PMID 24371822OA-icon.png] IRS1, TCF7L2, ADRB1, PPARG, and HHEX Polymorphisms Associated with Atherogenic Risk in Mexican Population


[PMID 22495925] Genetic polymorphisms inside and outside the MHC improve prediction of AS radiographic severity in addition to clinical variables.


[PMID 22703382] Effect of the Arg389Gly beta(1)-adrenoceptor polymorphism on plasma renin activity and heart rate, and the genotype-dependent response to metoprolol treatment.


[PMID 23065660] GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.


[PMID 24972470] ASSOCIATION OF β1 AND β3 ADRENERGIC RECEPTORS GENE POLYMORPHISMS WITH INSULIN RESISTANCE AND HIGH LIPID PROFILES RELATED TO TYPE 2 DIABETES AND METABOLIC SYNDROME