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Rs4149056

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Orientationplus
is asnp
is mentioned by
dbSNPrs4149056
PheGenIrs4149056
nextbiors4149056
hapmaprs4149056
1000 genomesrs4149056
hgdprs4149056
ensemblrs4149056
gopubmedrs4149056
geneviewrs4149056
scholarrs4149056
googlers4149056
pharmgkbrs4149056
gwascentralrs4149056
openSNPrs4149056
23andMers4149056
23andMe allrs4149056
SNP Nexus

SNPshotrs4149056
SNPdbers4149056
MSV3drs4149056
GeneSLCO1B1
Chromosome12
Orientationplus
GMAF0.123
Position21178615
ReferenceGRCh38 38.1/141
Max Magnitude3.2
Geno Mag Summary
(C;C) 3.2 17x myopathy risk for statin users
(C;T) 2.1 reduced breakdown of some drugs; 5x increased myopathy risk for statin users
(T;T) 0 normal
? (C;C) (C;T) (T;T) 28
CPMC Logo.png

This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB.
Additional information is available here

influences statin response

rs4149056, also known as 37041T>C or V174A, is a SNP in the SLCO1B1 gene, which encodes the 'organic anion transporting polypeptide 1B1' (OATP1B1) protein. This protein, found primarily in the liver, regulates the uptake of numerous drugs and natural compounds. The rs4149056(C) SNP defines the SLCO1B1*5 allele.

The rs4149056(C) allele gives rise to an amino acid change (from valine to alanine at residue 174) which has reduced uptake/transport activity. Therefore, drugs metabolized by OATP1B1 tend to build up to higher circulating concentrations than they would otherwise.[PMID 16758257].

The drugs known (or in some cases, thought) to be transported less well by the variant OATP1B1 protein encoded by the rs4149056(C) allele include:

[PMID 18650507] rs4363657 in nearly complete linkage disequilibrium with rs4149056 SNP (r2=0.97), which has been linked to statin metabolism. rs4149056(C) odds ratio for myopathy among 20,000 individuals taking either 40 or 80mg of simvastatin daily was 4.5 (CI: 2.6-7.7) per copy of the C allele, and 16.9 (CI: 4.7-61.1) in (C;C) as compared with (T;T) homozygotes.

The Gene Sherpa points out a 16x odds ratio for myopathy when taking statins and suggests fenofibrates might be a good alterative.

[PMID 19833260OA-icon.png] A study of ~500 individuals taking statins concluded that rs4149056(C), i.e. SLCO1B1*5, was associated with statin-induced side-effects, most likely somewhat correlated to the number of such alleles being carried.

[PMID 21178985OA-icon.png] A study of >4000 individuals with type 2 diabetes using routine prescribing data from the Electronic Medical Record in Tayside Scotland suggests high proportion rs4149056(C) homozygotes discontinue or reduce their doses of statins

23andMe blog discussion of this SNP

[PMID 23942138OA-icon.png] SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink

[PMID 19414484OA-icon.png] Genome-wide association meta-analysis for total serum bilirubin levels

OMIM604843
DescSOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY, MEMBER 1B1; SLCO1B1
Variant
Relatedalso

[PMID 19642078] Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients

[PMID 19901119OA-icon.png] Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects



[PMID 20837016] Loci from a genome-wide analysis of bilirubin levels are associated with gallstone risk and composition













[PMID 21243006] Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin

[PMID 21245207] Organic Anion Transporting Polypeptide 1B1: a Genetically Polymorphic Transporter of Major Importance for Hepatic Drug Uptake

OMIM601816
Desc
Variant
Relatedalso


[PMID 21630030] Frequency of the SLCO1B1 388A>G and the 521T>C polymorphism in Tanzania genotyped by a new LightCycler®-based method


[PMID 21851379OA-icon.png] The effects of a SNP in SLCO1B1 on the pharmacodynamics of pravastatin


[PMID 21992719OA-icon.png] SLCO1B1 rs4149056 polymorphism associated with statin-induced myopathy is differently distributed according to ethnicity in the Brazilian general population: Amerindians as a high risk ethnic group


[PMID 22189199] Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly


[PMID 22477766OA-icon.png] Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma concentration in HIV-infected adults


[PMID 22617227OA-icon.png] The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy


[PMID 22688219OA-icon.png] Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions


[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.


[PMID 19419973OA-icon.png] Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia.


[PMID 19474294OA-icon.png] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.


[PMID 19694740OA-icon.png] No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin.


[PMID 20139798] ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir.


[PMID 20389299OA-icon.png] Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.


[PMID 20973885] Organic anion transporter 1B1 (SLCO1B1) polymorphism and gallstone formation: High incidence of Exon4 CA genotype in female patients in North India.


[PMID 21360500OA-icon.png] Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.


[PMID 21386754OA-icon.png] Cerivastatin, genetic variants, and the risk of rhabdomyolysis.


[PMID 21928084] SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia.


[PMID 22136368] Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians.


[PMID 22580719] UGT1A1, SLCO1B1, and SLCO1B3 polymorphisms versus neonatal hyperbilirubinemia: is there an association?


GET Evidence
SLCO1B1-V174A
aa_change Val174Ala
aa_change_short V174A
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.112846
summary Increased plasma AUC with repaglinide.



Statin Response


[PMID 23233662OA-icon.png] Genome-wide study of methotrexate clearance replicates SLCO1B1

GWAS snp
PMID [PMID 22829776OA-icon.png]
Trait Sex hormone-binding globulin levels
Title A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
Risk Allele T
P-val 2E-8
Odds Ratio .03 [0.019-0.039] umol/L increase


[PMID 23652803] Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity and outcome in childhood acute lymphoblastic leukemia


[PMID 24459608OA-icon.png] SLCO1B1 Polymorphisms and Statin-Induced Myopathy


[PMID 22562052] SLCO1B1 *15 haplotype is associated with rifampin-induced liver injury.


[PMID 22711709OA-icon.png] Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel.


[PMID 22990751OA-icon.png] OATP1B1 polymorphism as a determinant of erythromycin disposition.


[PMID 23100282OA-icon.png] Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.


[PMID 23133420OA-icon.png] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.


[PMID 23183505] Possible gene-gender interaction between the SLCO1B1 polymorphism and statin treatment efficacy.


[PMID 23471819OA-icon.png] Direct and rapid genotyping of SLCO1B1 388A>G and 521T>C in human blood specimens using the SmartAmp-2 method.


[PMID 23480028] Fentanyl pharmacokinetics is not dependent on hepatic uptake by organic anion-transporting polypeptide 1B1 in human beings.


[PMID 23503447OA-icon.png] Discordant associations between SLCO1B1 521T-->C and plasma levels of ritonavir-boosted protease inhibitors in AIDS clinical trials group study A5146.


[PMID 23708174] Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy.


[PMID 23778707] International Transporter Consortium commentary on clinically important transporter polymorphisms.