The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells
Abstract
OBJECTIVES: SLCO1B1*5 and SLCO1B1*15 have been reported to reduce the clearance of pravastatin in healthy volunteers. However, there remains controversy in the effects of SLCO1B1*5 on the activity of OATP1B1 in vitro. In addition, the effect of SLCO1B1*15 on the function of OATP1B1 has not been studied using cDNA-expression systems. Object of the present study was to study the influence of SLCO1B1*5, *15 and *15+C1007G, a novel haplotype found in a patient with pravastatin-induced myopathy, on the functional properties of OATP1B1 by transient expression systems of HEK293 and HeLa cells using endogenous conjugates and statins as substrates. METHODS: Transporting assays for endogenous substrates were performed using tritium labeled estradiol-17beta-D-glucuronide and estrone-3-sulfate. Quantitation of pravastatin, atorvastatin, cerivastatin and simvastatin were carried out using HPLC tandem mass spectrometry. RESULTS: The transporting activities of cells expressing SLCO1B1*5, *15 and *15+C1007G decreased significantly but those of SLCO1B1*1b, *1a+C1007G and *1b+C1007G were not altered for all of the substrates tested except for simvastatin. Kinetic analysis of pravastatin and atorvastatin showed that Km values were not altered but Vmax values decreased significantly in cells expressing SLCO1B1*5, *15 and *15+C1007G. Immunocytochemical study showed that SLCO1B1*5, *15 and *15+C1007G proteins are localized not only at the plasma membrane but also in the intracellular space. CONCLUSIONS: These findings suggest that 521T>C, existing commonly in SLCO1B1*5, *15 and *15+C1007G, is the key single nucleotide polymorphism (SNP) that determines the functional properties of SLCO1B1*5, *15 and *15+C1007G allelic proteins and that decreased activities of these variant proteins are mainly caused by a sorting error produced by this SNP.
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A Novel Human Hepatic Organic Anion Transporting Polypeptide (OATP2)
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Identification of a Novel Gene Family Encoding Human Liver-specific Organic Anion Transporter LST-1
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Hepatic Uptake of Bilirubin and Its Conjugates by the Human Organic Anion Transporter SLC21A6
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Cited by
Shitara, Y., & Sugiyama, Y. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.03.003 · Cited by 576
The SLCO1B1*5Genetic Variant Is Associated With Statin-Induced Side Effects
Voora, D., Shah, S. H., Spasojevic, I., Ali, S., Reed, C. R., Salisbury, B. A., & Ginsburg, G. S. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.053 · Cited by 502
Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule?
Dobson, P. D., & Kell, D. B. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2438 · Cited by 475
SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid
Pasanen, M. K., Neuvonen, M., Neuvonen, P. J., & Niemi, M. (2006) · Pharmacogenetics and Genomics · doi:10.1097/01.fpc.0000230416.82349.90 · Cited by 470
Ramsey, L. B., Johnson, S. G., Caudle, K. E., Haidar, C. E., Voora, D., Wilke, R. A., Maxwell, W. D., McLeod, H. L., Krauss, R. M., Roden, D. M., et al. (2014) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2014.125 · Cited by 433
Metadata
- Authors
- Kameyama, Y., Yamashita, K., Kobayashi, K., Hosokawa, M., & Chiba, K.
- Venue
- Pharmacogenetics and Genomics
- Published
- 2005-07
- Volume
- 15
- Issue
- 7
- Pages
- 513-522
- ISSN
- 1744-6872 (ISSN-L)
- OpenAlex
- W2039141364
- Cited by
- 379
- References
- 19
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kameyama, Y., Yamashita, K., Kobayashi, K., Hosokawa, M., & Chiba, K. (2005). Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenetics and Genomics. https://doi.org/10.1097/01.fpc.0000170913.73780.5f
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