ArticlePharmaceutical research2021
The Effect of Single Nucleotide Variations in the Transmembrane Domain of OATP1B1 on in vitro Functionality.
Article in Pharmaceutical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Impact of Pharmacogenetics on Pharmacokinetics of First-Line Antituberculosis Drugs in the HIRIF Trial.The Journal of infectious diseases · 2025Trial
- PBPK Modeling of Coproporphyrin I Reveals Frailty-Associated Changes in Hepatic OATP1B1 Function in Chinese Adults.Clinical pharmacokinetics · 2026Article
- Pharmacogenetics of Mycophenolic Acid in Patients of African Descent: Underrepresentation of African Data.Clinical and translational science · 2026Review
- Structural basis for prostaglandin and drug transport via SLCO2A1.Nature communications · 2026Article
- Impacts of Pharmacokinetic Gene Polymorphisms on Steady-State Plasma Concentrations of Simvastatin in Thai Population.Clinical and translational science · 2025Article
- Cryo-EM structures of human organic anion transporting polypeptide OATP1B1.Cell research · 2023Article
- Functional Characterization of SixMolecular pharmaceutics · 2023Article
- Should we test for SLCO1B1 genotype before prescribing statins?-a discussion of clinical trial results.Annals of translational medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeOrganic Anion Transporting Polypeptide 1B1 (OATP1B1) mediates hepatic influx and clearance of many drugs, including statins. The SLCO1B1 gene is highly polymorphic and its function-impairing variants can predispose patients to adverse effects. The effects of rare genetic variants of SLCO1B1 are mainly unexplored. We examined the impact of eight naturally occurring rare variants and the well-known SLCO1B1 c.521C > T (V174A) variant on in vitro transport activity, cellular localization and abundance.
methodsTransport of rosuvastatin and 2,7-dichlorofluorescein (DCF) in OATP1B1 expressing HEK293 cells was measured to assess changes in activity of the variants. Immunofluorescence and confocal microscopy determined the cellular localization of OATP1B1 and LC-MS/MS based quantitative targeted absolute proteomics analysis quantified the amount of OATP1B1 in crude membrane fractions.
resultsAll studied variants, with the exception of P336R, reduced protein abundance to varying degree. V174A reduced protein abundance the most, over 90% compared to wild type. Transport function was lost in G76E, V174A, L193R and R580Q variants. R181C decreased activity significantly, while T345M and L543W retained most of wild type OATP1B1 activity. P336R showed increased activity and H575L decreased the transport of DCF significantly, but not of rosuvastatin. Decreased activity was interrelated with lower absolute protein abundance in the studied variants.
conclusionsTransmembrane helices 2, 4 and 11 appear to be crucial for proper membrane localization and function of OATP1B1. Four of the studied variants were identified as loss-of-function variants and as such could make the individual harboring these variants susceptible to altered pharmacokinetics and adverse effects of substrate drugs.
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