Variants in the SLCO1B3 Gene: Interethnic Distribution and Association with Paclitaxel Pharmacokinetics View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-01

AUTHORS

NF Smith, S Marsh, TJ Scott‐Horton, A Hamada, S Mielke, K Mross, WD Figg, J Verweij, HL McLeod, A Sparreboom

ABSTRACT

To explore retrospectively the relationships between paclitaxel pharmacokinetics and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP)1B3. Accumulation of [(3)H]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP. The 334T>G (Ser112Ala), 699G>A (Met233Ile), and 1564G>T (Gly522Cys) loci of SLCO1B3 were screened in 475 individuals from five ethnic groups and 90 European Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of transporting paclitaxel to a significant extent (P=0.003). The 334T>G and 699G>A SNPs were less common in the African-American and Ghanaian populations (P<0.000001). Paclitaxel pharmacokinetics were not associated with the studied SNPs or haplotypes (P>0.3). The studied SNPs in SLCO1B3 appear to play a limited role in the disposition of paclitaxel, although their clinical significance in other ethnic populations remains to be investigated. More... »

PAGES

76-82

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.clpt.6100011

DOI

http://dx.doi.org/10.1038/sj.clpt.6100011

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1005218085

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17186002


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