Human MDR1 polymorphism: G2677T/A and C3435T have no effect on MDR1 transport activities
Human MDR1 polymorphism: G2677T/A and C3435T have no effect on MDR1 transport activities
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DOI：
10.1016/s0006-2952(03)00178-3
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发表时间：
2003-06-01
影响因子：
5.8
通讯作者：
Nakayama, K
中科院分区：
文献类型：
--
作者：
Morita, N;Yasumori, T;Nakayama, K
人类多药耐药性 I (MDR1) 基因中两个最常见的单核苷酸多态性 (SNP) 是 2677G/T/A (893Ala/Ser/Thr) 和 3435C/T（无氨基酸取代）。在这项研究中，六种形式的带有 SNP 的 MDR1 cDNA 在 LLC-PK1 细胞中表达，并测定了它们的转运活性。使用 Flp 重组酶在已建立的细胞系中表达几乎相同数量的重组 MDR1 蛋白，该酶将感兴趣的基因整合到特定的基因组位置。检查了四种结构不同的化合物：维拉帕米、地高辛、长春碱和环孢菌素 A 的跨细胞转运活性和细胞内积累。在表达五种多态性类型的 MDR1 cDNA（2677G/3435T、2677A/3435C、2677A/3435T、2677T/3435C、2677T/3435T）的细胞和表达野生型（2677G/3435C）的细胞之间没有观察到显着差异。这些结果表明，两个经常观察到的MDR1 SNP对体外LLC-PK1细胞中表达的N4DR1蛋白的转运活性没有影响，其他遗传或环境因素可能控制MDR1的表达和MDR1的体内活性。 (C) 2003 Elsevier Science Inc. 保留所有权利。
The two most frequently observed single nucleotide polymorphisms (SNPs) of the human multidrug resistance I (MDR1) gene are 2677G/T/A (893Ala/Ser/Thr) and 3435C/T (no amino acid substitution). In this study, six forms of MDR1 cDNAs with the SNPs were expressed in LLC-PK1 cells and their transport activities were determined. Nearly identical amounts of the recombinant MDR1 proteins were expressed in the established cell lines using the Flp recombinase, which integrates a gene of interest at a specific genomic location. Four structurally diverse compounds: verapamil, digoxin, vinblastine and cyclosporin A, were examined for transcellular transport activities and intracellular accumulation. No significant differences were observed between cells expressing five polymorphic types of the MDR1 cDNAs (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) and cells expressing the wild-type (2677G/3435C). These results suggested that the two frequently observed MDR1 SNPs had no effect on the transport activities of N4DR1 proteins expressed in LLC-PK1 cells in vitro, and other genetic or environmental factors might control the expression of MDR1 and the in vivo activity of MDR1. (C) 2003 Elsevier Science Inc. All rights reserved.