SLCO1B1 V174A - GET-Evidence

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(SLCO1B1 Val174Ala)

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Short summary

Increased plasma AUC with repaglinide.

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
Clinical importance
Severity -
Treatability -
Penetrance -


Insufficiently evaluated pharmacogenetic

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

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • C @ chr12:21331549: 11.3% (1214/10758) in EVS
  • C @ chr12:21222815: 7.8% (10/128) in GET-Evidence
  • Frequency shown in summary reports: 11.3% (1214/10758)


Added in this revision:

Zaïr ZM, Eloranta JJ, Stieger B, Kullak-Ublick GA. Pharmacogenetics of OATP (SLC21/SLCO), OAT and OCT (SLC22) and PEPT (SLC15) transporters in the intestine, liver and kidney. Pharmacogenomics. 2008 May;9(5):597-624. Review. PubMed PMID: 18466105.







Other external references

  • Serum bilirubin levels (rs4149056-C)
    Johnson 4-May-09 in Hum Mol Genet
    OR or beta: 0.05 [0.03-0.07] umol/l increase in l
    Risk allele frequency: 0.15
    p-value: 7.00E-13
    Initial sample: 9,264 individuals
    Replication sample: NR
  • Response to statin therapy (rs4149056-C)
    The SEARCH Collaborative Group 23-Jul-08 in N Engl J Med
    OR or beta: 4.5 [2.60-7.70]
    Risk allele frequency: 0.13
    p-value: 2.00E-09
    Initial sample: 85 cases, 90 controls
    Replication sample: 19,856 individuals
  • [Organ Transplantation]
    [mycophenolate mofetil; mycophenolic acid; sirolimus; tacrolimus]
    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
  • [pravastatin]
    Associated with increased pravastatin plasma AUC.
  • 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.
  • [Muscular Diseases; Myopathy, Central Core]
    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.
  • [atorvastatin; fluvastatin; pravastatin; rosuvastatin; simvastatin]
    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.
  • [Myopathy, Central Core]
    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.; Web Resource:
  • Variant with C allele showed reduced cell surface expression
  • [pravastatin]
    Variant with C allele had reduced transport, relative to variant with T allele (based upon lower plasma AUC) of pravastatin; PubMed ID:17177112
  • [nateglinide]
    Variant with C allele showed NO plasma AUC of nateglinide relative to T allele, in contrast to repaglinide
  • [repaglinide]
    Variant with C allele showed increased plasma AUC of repaglinide relative to T
  • [atorvastatin]
    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.
  • [Hypercholesterolemia; Muscular Diseases; Myalgia unspecified]
    [atorvastatin; pravastatin; simvastatin]
    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
  • [Precursor Cell Lymphoblastic Leukemia-Lymphoma]
    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

Other in silico analyses

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 2

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Gene search

"GENE" or "GENE A123C":

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