TY - JOUR
T1 - Variants in the SLCO1B3 gene
T2 - Interethnic distribution and association with paclitaxel pharmacokinetics
AU - Smith, N. F.
AU - Marsh, S.
AU - Scott-Horton, T. J.
AU - Hamada, A.
AU - Mielke, S.
AU - Mross, K.
AU - Figg, W. D.
AU - Verweij, J.
AU - McLeod, H. L.
AU - Sparreboom, A.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33845975969&partnerID=8YFLogxK
U2 - 10.1038/sj.clpt.6100011
DO - 10.1038/sj.clpt.6100011
M3 - Article
C2 - 17186002
AN - SCOPUS:33845975969
SN - 0009-9236
VL - 81
SP - 76
EP - 82
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 1
ER -