Variants in the SLCO1B3 gene: Interethnic distribution and association with paclitaxel pharmacokinetics

N. F. Smith, S. Marsh, T. J. Scott-Horton, A. Hamada, S. Mielke, K. Mross, W. D. Figg, J. Verweij, H. L. McLeod, A. Sparreboom*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

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 [3H]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.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume81
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

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