SLCO1B3基因变异：种族间分布及其与紫杉醇药代动力学的关联
Variants in the SLCO1B3 gene: interethnic distribution and association with paclitaxel pharmacokinetics.
作者信息
Smith N F, Marsh S, Scott-Horton T J, Hamada A, Mielke S, Mross K, Figg W D, Verweij J, McLeod H L, Sparreboom A
机构信息
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
出版信息
Clin Pharmacol Ther. 2007 Jan;81(1):76-82. doi: 10.1038/sj.clpt.6100011.
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<0.000001). 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.
为了回顾性探究紫杉醇药代动力学与溶质载体有机阴离子转运体家族成员1B3（SLCO1B3）中三个已知的非同义单核苷酸多态性（SNP）之间的关系，SLCO1B3是编码有机阴离子转运多肽（OATP）1B3的基因。在注射了Oatp1b2、OATP1A2、OATP1B1、OATP1B3、OAT1、OAT3、OCT1和NTCP的cRNA的非洲爪蟾卵母细胞中研究了[³H]紫杉醇的蓄积情况。在来自五个种族的475名个体以及90名接受紫杉醇治疗的欧洲白种癌症患者中筛查了SLCO1B3的334T>G（Ser112Ala）、699G>A（Met233Ile）和1564G>T（Gly522Cys）位点。只有OATP1B3能够在很大程度上转运紫杉醇（P = 0.003）。334T>G和699G>A这两个SNP在非裔美国人和加纳人群中不太常见（P < 0.000001）。紫杉醇药代动力学与所研究的SNP或单倍型无关（P > 0.3）。SLCO1B3中所研究的SNP在紫杉醇的处置中似乎起有限作用，尽管它们在其他种族人群中的临床意义仍有待研究。
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