Variants in the SLCO1B3 gene:: Interethnic distribution and association with paclitaxel pharmacokinetics
Variants in the SLCO1B3 gene:: Interethnic distribution and association with paclitaxel pharmacokinetics
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DOI：
10.1038/sj.clpt.6100011
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发表时间：
2007-01-01
影响因子：
6.7
通讯作者：
Sparreboom, A.
中科院分区：
文献类型：
--
作者：
Smith, N. F.;Marsh, S.;Sparreboom, A.
目的：探讨紫杉醇药代动力学与编码有机阴离子转运多肽(OATP1B3)基因SLCO1B3的3个非同义单核苷酸多态(SNPs)的关系。研究了OatP1b2、OATP1A2、OATP1B1、OATP1B3、OAT1、OAT3、OCT1和INITCP基因在非洲爪哇卵母细胞中[H-3]紫杉醇的积累。对来自5个民族的475名个体和90例接受紫杉醇治疗的欧洲高加索癌症患者进行了SLCO1B3基因334T>；G(Ser112Ala)、699G>；A(Met233 Lle)和1564G>；T(Gly522Cys)的筛查。只有OATP1B3能在很大程度上转运紫杉醇(P=0.003)。334T>；G和699G；A SNP在非洲裔美国人和加纳人中不太常见(P<；0.000001)。紫杉醇的药代动力学与所研究的SNPs或单倍型无关(P>；0.3)。SLCO1B3中已研究的SNPs在紫杉醇的处置中发挥的作用似乎有限，尽管它们在其他民族人群中的临床意义仍有待调查。
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 [H-3]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and INITCP. The 334T > G (Ser112Ala), 699G > A (Met233lle), 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 Africa n-American and Ghanaian populations (P < 0.000001). Paclitaxel pharmacokinetics were riot 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.