{{Rsnum
|rsid=4149056
|Gene=SLCO1B1
|Chromosome=12
|position=21178615
|Orientation=plus
|ReferenceAllele=T
|MissenseAllele=C
|GMAF=0.123
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=SLCO1B1
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 0.9 | 28.3 | 70.8
| HCB | 1.5 | 24.1 | 74.5
| JPT | 2.7 | 18.6 | 78.8
| YRI | 0.0 | 1.4 | 98.6
| ASW | 1.8 | 7.0 | 91.2
| CHB | 1.5 | 24.1 | 74.5
| CHD | 2.8 | 18.3 | 78.9
| GIH | 0.0 | 4.0 | 96.0
| LWK | 0.0 | 4.5 | 95.5
| MEX | 0.0 | 17.2 | 82.8
| MKK | 1.9 | 19.2 | 78.8
| TSI | 3.9 | 35.3 | 60.8
| HapMapRevision=28
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/Simvastatin.aspx
}}
influences [[statin]] response
*[[rs72559745]] (SLCO1B1*1)	AA	AA
*[[rs56061388]] (SLCO1B1*3)	TT	TT
*[[rs4149056]] (SLCO1B1*5)	TT	TT
*[[rs55901008]] (SLCO1B1*6)	TT	TT
[[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:

*Several cholesterol lowering [[statins]], generally leading to reduced inhibitory effects on liver cholesterol synthesis and possibly worse side effects, by such drugs as:
**[[simvastatin]]
**[[pravastatin]]
**[[rosuvastatin]]
**[[pitavastatin]]
*[[fexofenadine]]
*[[repaglinide]]
*[[methotrexate]]
*the SN-38 active metabolite of [[irinotecan]]
*[[rifampicin]]
*[[caspofungin]]
*[[lopinavir]]

{{PMID|18650507}} [[rs4363657]] in nearly complete linkage disequilibrium with [[rs4149056]] SNP (r<sup>2</sup>=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.

[http://thegenesherpa.blogspot.com/2008/08/muscle-pain-from-statins-time-for.html The Gene Sherpa] points out a 16x odds ratio for myopathy when taking [[statins]] and suggests fenofibrates might be a good alterative.

{{PMID|19833260|OA=1
}} 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|21178985|OA=1
}} 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 

[http://blog.23andme.com/2008/07/24/snpwatch-gene-variant-may-increase-risk-for-rare-side-effect-of-cholesterol-lowering-drugs/ 23andMe blog] discussion of this SNP

{{PMID|23942138|OA=1
}} SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink
{{PMID Auto
|PMID=19414484
|Title=Genome-wide association meta-analysis for total serum bilirubin levels
|OA=1
}}

{{omim
|desc=SOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY, MEMBER 1B1; SLCO1B1
|id=604843
|rsnum=4149056
}}
{{PMID Auto
|PMID=19642078
|Title=Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients
}}
{{PMID Auto
|PMID=19901119
|Title=Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects
|OA=1
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SCLO1B1: SLCO1B1*15 defined by rs2306283 Asn130Asp (338A>G) and rs4149056 Val174Ala (521T>C)
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19890249
|Annotation=Risk or phenotype-associated allele: SLCO1B1*15 defined by rs2306283 Asn130Asp (338A>G) and rs4149056 Val174Ala (521T>C). Phenotype: SLCO1B1*15 allele was associated with higher mycophenolic acid (MPA) AUC(0-12 hours) (p = 0.0246) and lower ratio of MPAG (MPA glucuronide)/MPA (p = 0.0267), but no association with MPAG AUC(0-9 h). Study size: 70. Study population/ethnicity: Caucasian cohort from the SOPHIE study cotreated with mycophenylate mofetil (MMF) and either sirolimus or tacrolimus. Significance metric(s): p < 0.03. Type of association: GN; PK
|Drugs=mycophenolate mofetil; mycophenolic acid; sirolimus; tacrolimus
|Drug Classes=
|Diseases=Organ Transplantation
|Curation Level=Curated
|PharmGKB Accession ID=PA165109803
}}

{{PMID Auto
|PMID=20837016
|Title=Loci from a genome-wide analysis of bilirubin levels are associated with gallstone risk and composition
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1:V174A
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/slco1b1/variant.jsp
|Annotation=Associated with increased pravastatin plasma AUC.
|Drugs=pravastatin
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145159
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1: V174A
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18466105
|Annotation=Studies into the effect of the 521T>C (V174A) SNP in SLCO1B1 yielded discrepancies in the transport data of estradiol-17?-D-glucuronide and estrone-3-sulfate.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA161748444
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18650507
|Annotation=This variant in the SLCO1B1 gene is strongly associated with an increased risk of statin-induced myopathy. This study also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin.
|Drugs=simvastatin
|Drug Classes=HMG COA REDUCTASE INHIBITORS
|Diseases=Muscular Diseases; Myopathy, Central Core
|Curation Level=Curated
|PharmGKB Accession ID=PA162356046
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1:c.521T>C, SLCO1B1:p.Val174Ala
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18794729
|Annotation=The cholesterol synthesis rate was higher in CC individuals than in TT individuals. There was no association between this SNP and the short-term effects of statins on cholesterol synthesis rates.
|Drugs=atorvastatin; fluvastatin; pravastatin; rosuvastatin; simvastatin
|Drug Classes=HMG COA REDUCTASE INHIBITORS
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA162356181
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18650507; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: SLCO1B1 Variants and Statin-Induced Myopathy--A Genomewide Study. (Initial Sample Size: 85 cases, 90 controls; Replication Sample Size: 19,856 individuals); (Region: 12p12.1; Reported Gene(s): SLCO1B1; Risk Allele: rs4149056-C); (p-value= 0.000000002).This variant is associated with Myopathy.
|Drugs=
|Drug Classes=
|Diseases=Myopathy, Central Core
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740859
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1:521T>C, SLCO1B1:*5
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:11477075
|Annotation=Variant with C allele showed reduced cell surface expression
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164891482
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1:521T>C, SLCO1B1:*5
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:12811365; PubMed ID:17177112
|Annotation=Variant with C allele had reduced transport, relative to variant with T allele (based upon lower plasma AUC) of pravastatin
|Drugs=pravastatin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164891481
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1:521T>C, SLCO1B1:*5
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18187595
|Annotation=Variant with C allele showed NO plasma AUC of nateglinide relative to T allele, in contrast to repaglinide
|Drugs=nateglinide
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164891484
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1:521T>C, SLCO1B1:*5
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18187595
|Annotation=Variant with C allele showed increased plasma AUC of repaglinide relative to T
|Drugs=repaglinide
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164891483
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1 521T>C; Val174Ala; SLCO1B1*5
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19374892
|Annotation=In a study of 16 subjects rifampicin increased atorvastatin plasma concentration in accordance with SLCO1B1 521T>C genotype. Rifampicin pharmacokinetics were not altered by SLCO1B1 genotype.
|Drugs=atorvastatin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164925732
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=SLCO1B1*5, c.521T>C. mRNA 616T>G, p.Val174Ala
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19833260
|Annotation=Risk or phenotype-associated allele: SLCO1B1*5 allele, defined by rs4149056 (521T>C, Val174Ala). Phenotype: SLCO1B1*5 allele (rs4149056, V174A) was associated with the adverse events from statins (chi-square = 4.2, p = 0.03, FDR = 0.24), with greatest risk with simvastatin. There were significantly more females (66%) with adverse events than females without adverse events (50%) (p < 0.01). Among subjects with adverse effects (n = 99), females bore greater risk of adverse events (OR = 2.0, p = 0.004). In multivariate analysis adjusted for race, female sex (OR = 2.2, p = 0.001) and SLCO1B1*5 genotype (OR = 1.7, p = 0.03) were independently associated with adverse events to statins (p < 0.05 for both). Simvastatin plasma concentration was positively correlated with SLCO1B1*5 both at 20 mg (p = 0.006) and 80 mg (p = 0.03). Study size: 452. Study population/ethnicity: Hypercholesterolemia outpatients given 1 of 3 statins (atorvastatin, simvastatin, or pravastatin) between 2001 and 2002 Significance metric(s): OR (1.7 - 2.2), p < 0.05 Type of association: CO; GN; PK; ADR
|Drugs=atorvastatin; pravastatin; simvastatin
|Drug Classes=
|Diseases=Hypercholesterolemia; Muscular Diseases; Myalgia unspecified
|Curation Level=Curated
|PharmGKB Accession ID=PA165110263
}}

{{PharmGKB
|RSID=rs4149056
|Name_s=OATP1B1: c.521T>C; mRNA 616T>C, p.Val174Ala
|Gene_s=SLCO1B1
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19901119
|Annotation=Risk or phenotype-associated allele: C allele (174Ala). Phenotype: Genome-wide analysis of 398,699 germline SNPs showed association of the rs4149056 C allele (174Ala) with methotrexate (MTX) plasma clearance. Study size: 434 (discovery cohort), 206 (independent validation cohort). Study population/ethnicity: Multiethnic children (5.92 median age , 1.02-18.85 range) with ALL given 3,014 courses of methotrexate at 2-5 g/m(2) enrolled in Tennessee. Significance metric(s): p = 1.9 x 10(-7) (n = 434); p = 1.2 x 10(-7) (n = 206). Type of association: CO; GN; PK
|Drugs=methotrexate
|Drug Classes=
|Diseases=Precursor Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA165110328
}}
{{PMID Auto
|PMID=21243006
|Title=Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin
}}
{{PMID Auto
|PMID=21245207
|Title=Organic Anion Transporting Polypeptide 1B1: a Genetically Polymorphic Transporter of Major Importance for Hepatic Drug Uptake
}}

{{omim
|id=601816
|rsnum=4149056
}}

{{PMID Auto
|PMID=21630030
|Title=Frequency of the SLCO1B1 388A&gt;G and the 521T&gt;C polymorphism in Tanzania genotyped by a new LightCycler®-based method
}}

{{PMID Auto
|PMID=21851379
|Title=The effects of a SNP in SLCO1B1 on the pharmacodynamics of pravastatin
|OA=1
}}

{{PMID Auto
|PMID=21992719
|Title=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
|OA=1
}}

{{PMID Auto
|PMID=22189199
|Title=Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly
}}

{{PMID Auto
|PMID=22477766
|Title=Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma concentration in HIV-infected adults
|OA=1
}}

{{PMID Auto
|PMID=22617227
|Title=The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy
|OA=1
}}

{{PMID Auto
|PMID=22688219
|Title=Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions
|OA=1
}}

{{PMID Auto
|PMID=18547414
|Title=Genotyping panel for assessing response to cancer chemotherapy.
|OA=1
}}

{{PMID Auto
|PMID=19419973
|Title=Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia.
|OA=1
}}

{{PMID Auto
|PMID=19474294
|Title=Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
|OA=1
}}

{{PMID Auto
|PMID=19694740
|Title=No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin.
|OA=1
}}

{{PMID Auto
|PMID=20139798
|Title=ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir.
}}

{{PMID Auto
|PMID=20389299
|Title=Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.
|OA=1
}}

{{PMID Auto
|PMID=20973885
|Title=Organic anion transporter 1B1 (SLCO1B1) polymorphism and gallstone formation: High incidence of Exon4 CA genotype in female patients in North India.
}}

{{PMID Auto
|PMID=21360500
|Title=Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.
|OA=1
}}

{{PMID Auto
|PMID=21386754
|Title=Cerivastatin, genetic variants, and the risk of rhabdomyolysis.
|OA=1
}}

{{PMID Auto
|PMID=21928084
|Title=SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia.
}}

{{PMID Auto
|PMID=22136368
|Title=Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians.
}}

{{PMID Auto
|PMID=22580719
|Title=UGT1A1, SLCO1B1, and SLCO1B3 polymorphisms versus neonatal hyperbilirubinemia: is there an association?
}}

{{GET Evidence
|gene=SLCO1B1
|aa_change=Val174Ala
|aa_change_short=V174A
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs4149056
|overall_frequency_n=1214
|overall_frequency_d=10758
|overall_frequency=0.112846
|n_genomes=8
|n_genomes_annotated=0
|n_haplomes=9
|n_articles=9
|n_articles_annotated=9
|in_gwas=Y
|in_pharmgkb=Y
|nblosum100=2
|autoscore=2
|webscore=N
|summary_short=Increased plasma AUC with repaglinide.
}}

[[Statin Response]]

{{PMID Auto
|PMID=23233662
|Title=Genome-wide study of methotrexate clearance replicates SLCO1B1
|OA=1
}}

{{PMID Auto GWAS
  |PMID=22829776
  |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.
  |RiskAllele=T
  |Pval=2E-8
  |OR=.03
  |ORtxt=[0.019-0.039] umol/L increase
  |OA=1
}}

{{PMID Auto
|PMID=23652803
|Title=Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity and outcome in childhood acute lymphoblastic leukemia
}}

{{PMID Auto
|PMID=24459608
|Title=SLCO1B1 Polymorphisms and Statin-Induced Myopathy
|OA=1
}}

{{PMID Auto
|PMID=22562052
|Title=SLCO1B1 *15 haplotype is associated with rifampin-induced liver injury.
}}

{{PMID Auto
|PMID=22711709
|Title=Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel.
|OA=1
}}

{{PMID Auto
|PMID=22990751
|Title=OATP1B1 polymorphism as a determinant of erythromycin disposition.
|OA=1
}}

{{PMID Auto
|PMID=23100282
|Title=Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.
|OA=1
}}

{{PMID Auto
|PMID=23133420
|Title=Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
|OA=1
}}

{{PMID Auto
|PMID=23183505
|Title=Possible gene-gender interaction between the SLCO1B1 polymorphism and statin treatment efficacy.
}}

{{PMID Auto
|PMID=23471819
|Title=Direct and rapid genotyping of SLCO1B1 388A>G and 521T>C in human blood specimens using the SmartAmp-2 method.
|OA=1
}}

{{PMID Auto
|PMID=23480028
|Title=Fentanyl pharmacokinetics is not dependent on hepatic uptake by organic anion-transporting polypeptide 1B1 in human beings.
}}

{{PMID Auto
|PMID=23503447
|Title=Discordant associations between SLCO1B1 521T-->C and plasma levels of ritonavir-boosted protease inhibitors in AIDS clinical trials group study A5146.
|OA=1
}}

{{PMID Auto
|PMID=23708174
|Title=Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy.
}}

{{PMID Auto
|PMID=23778707
|Title=International Transporter Consortium commentary on clinically important transporter polymorphisms.
}}

{{PMID Auto
|PMID=25124723
|Title=SLC19A1, SLC46A1 and SLCO1B1 Polymorphisms As Predictors Of Methotrexate-Related Toxicity In Portuguese Rheumatoid Arthritis Patients
}}

{{PMID Auto
|PMID=24865931
|Title=Combined effects of the UGT1A1 and OATP2 gene polymorphisms as major risk factor for unconjugated hyperbilirubinemia in Indian neonates
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}