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:
- the SN-38 active metabolite of irinotecan
[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.
[PMID 19833260] 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] 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 19414484] Genome-wide association meta-analysis for total serum bilirubin levels
[PMID 19642078] Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients
[PMID 19901119] 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
[PMID 21630030] Frequency of the SLCO1B1 388A>G and the 521T>C polymorphism in Tanzania genotyped by a new LightCycler®-based method
[PMID 21851379] The effects of a SNP in SLCO1B1 on the pharmacodynamics of pravastatin
[PMID 21992719] 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 22477766] Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma concentration in HIV-infected adults
[PMID 22617227] The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy
[PMID 22688219] Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions
[PMID 18547414] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 19419973] Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 19694740] 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 20389299] 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 21360500] Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.
[PMID 21386754] 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?
|qualified_impact||Insufficiently evaluated pharmacogenetic|
|summary||Increased plasma AUC with repaglinide.|
[PMID 23233662] Genome-wide study of methotrexate clearance replicates SLCO1B1
|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.|
|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