ArticlePharmacogenetics and genomics2011
Identification of novel functional organic anion-transporting polypeptide 1B3 polymorphisms and assessment of substrate specificity.
Article in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 89 citations in OpenAlex.
- A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers.BMC cancer · 2016Trial
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- Impact of SLCO1B3 767G>C (rs60140950) polymorphism on paclitaxel response in Iraqi women with breast cancer.Journal of Taibah University Medical Sciences · 2026Article
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- Organic anion transporting polypeptides: Pharmacology, toxicology, structure, and transport mechanisms.Pharmacological reviews · 2025Review
- Elucidating nonlinear pharmacokinetics of telmisartan: Integration of target-mediated drug disposition and OATP1B3-mediated hepatic uptake in a physiologically based model.CPT: pharmacometrics & systems pharmacology · 2024Article
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- Structure of human drug transporters OATP1B1 and OATP1B3.Nature communications · 2023Article
- Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy.JCI insight · 2023Article
- Association of Drug-Metabolizing Enzyme and Transporter Gene Polymorphisms and Lipid-Lowering Response to Statins in Thai Patients with Dyslipidemia.Pharmacogenomics and personalized medicine · 2022Article
- Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications.Pharmaceutics · 2021Review
- Late response to rosuvastatin and statin-related myalgia due toAnnals of translational medicine · 2021Article
- Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion-transporting polypeptides.The Journal of biological chemistry · 2020Review
- Review
- Impact of SLCO1B1 Genetic Variation on Rosuvastatin Systemic Exposure in Pediatric Hypercholesterolemia.Clinical and translational science · 2020Observational
- The Emerging Role of the SLCO1B3 Protein in Cancer Resistance.Protein and peptide letters · 2020Review
- Organic Anion Transporting Polypeptides: Emerging Roles in Cancer Pharmacology.Molecular pharmacology · 2019Review
- The Role of Next-Generation Sequencing in Pharmacogenetics and Pharmacogenomics.Cold Spring Harbor perspectives in medicine · 2019Review
- OATP1B3 (699G>A) and CYP2C9*2, *3 significantly influenced the transport and metabolism of glibenclamide and glipizide.Scientific reports · 2018Article
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
objectiveThe uptake carrier organic anion-transporting polypeptide 1B3 (OATP1B3, gene SLCO1B3) is involved in the hepatic clearance of xenobiotics including statins, taxanes, and mycophenolic acid. We thought to assess the SLCO1B3 coding region for yet unidentified polymorphisms and to analyze their functional relevance.
methodsWe used DNA of ethnically diverse individuals for polymerase chain reaction, and determined polymorphisms by sequencing or temperature-dependent capillary electrophoresis. We then created variant OATP1B3 expression plasmids by site-directed mutagenesis, which were transiently expressed and functionally characterized in human cervical carcinoma (HeLa) cells using radiolabeled substrates.
resultsWe identified six nonsynonymous polymorphisms including novel variants such as 439A>G (Thr147Ala), 767G>C (Gly256Ala), 1559A>C (His520Pro), and 1679T>C (Val560Ala). Allelic frequencies occurred to be ethnicity-dependent, with the latter observed only in African-Americans (3.6%). After expression in HeLa cells, His520Pro, Val560Ala, and Met233Ile or Met233Ile_Ser112Ala haplotype variants showed decreased uptake activity compared with wild type for cholecystokinin-8 and rosuvastatin, but not for atorvastatin. Kinetic cholecystokinin-8 analysis showed reduced Vmax without altering Km. His520Pro and Val560Ala exhibited decreased total and plasma membrane protein expressions. Val560 mapped onto a structural model of OATP1B3 showed that this is a key region for substrate-transporter interaction. His520 resides in a predicted extracellular region thought to be critical to the pH-dependent component of OATP1B3 activity. Loss of activity at pH 7.4 and 8.0 relative to pH 6.5 was significantly greater for the Pro520 variant.
conclusionOATP1B3 polymorphisms that result in altered expression, substrate specificity, and pH-dependent activity may be of potential relevance to hepatic clearance of substrate drugs in vivo.
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