Variants in the SLCO1B3 Gene: Interethnic Distribution and Association with Paclitaxel Pharmacokinetics
Copyright policy )Variants in the SLCO1B3 Gene: Interethnic Distribution and Association with Paclitaxel Pharmacokinetics
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 (P0.3). 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.
- University of Mary United States
- University Medical Center Freiburg Germany
- National Cancer Institute United States
- Erasmus University Medical Center Netherlands
- Washington University in St. Louis United States
Dose-Response Relationship, Drug, Genotype, Paclitaxel, Racial Groups, In Vitro Techniques, Organic Anion Transporters, Sodium-Independent, Antineoplastic Agents, Phytogenic, Polymorphism, Single Nucleotide, Solute Carrier Organic Anion Transporter Family Member 1B3, Xenopus laevis, EMC MM-03-86-08, Oocytes, Animals, Humans, Female, Retrospective Studies
Dose-Response Relationship, Drug, Genotype, Paclitaxel, Racial Groups, In Vitro Techniques, Organic Anion Transporters, Sodium-Independent, Antineoplastic Agents, Phytogenic, Polymorphism, Single Nucleotide, Solute Carrier Organic Anion Transporter Family Member 1B3, Xenopus laevis, EMC MM-03-86-08, Oocytes, Animals, Humans, Female, Retrospective Studies
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