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Variants in the SLCO1B3 Gene: Interethnic Distribution and Association with Paclitaxel Pharmacokinetics
Author(s) -
Smith NF,
Marsh S,
ScottHorton TJ,
Hamada A,
Mielke S,
Mross K,
Figg WD,
Verweij J,
McLeod HL,
Sparreboom A
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100011
Subject(s) - paclitaxel , single nucleotide polymorphism , pharmacokinetics , haplotype , organic anion transporting polypeptide , pharmacology , medicine , biology , gene , genetics , transporter , cancer , genotype
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 <0.1). 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. Clinical Pharmacology & Therapeutics (2007) 81 , 76–82. doi: 10.1038/sj.clpt.6100011