Modulation of human placental P-glycoprotein expression and activity by MDR1 gene polymorphisms.
Modulation of human placental P-glycoprotein expression and activity by MDR1 gene polymorphisms.
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DOI：
10.1016/j.bcp.2009.10.026
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发表时间：
2010-03-15
影响因子：
5.8
通讯作者：
Ahmed, Mahmoud S.
中科院分区：
文献类型：
--
作者：
Hemauer, Sarah J.;Nanovskaya, Tatiana N.;Abdel-Rahman, Sherif Z.;Patrikeeva, Svetlana L.;Hankins, Gary D. V.;Ahmed, Mahmoud S.
ABC 转运蛋白 P-糖蛋白是 MDR1 基因的产物，其在人胎盘中的功能是将异生素从组织中挤出，从而减少胎儿的暴露。本研究的目的是检查 MDR1 基因中的三种多态性对胎盘 P-gp 表达和活性的影响。在检查的 199 个足月胎盘中，C1236T 变体与 P-gp 蛋白表达比野生型降低 11% 相关，而 C3435T 和 G2677T/A 变体均与 16% 降低相关 (p < 0.05)。 C1236T 和 C3435T 变异等位基因 (TT) 的纯合子与原型底物 [3H]-紫杉醇的胎盘 P-gp 转运活性分别增加 42% 和 47% (p = 0.04 和 p = 0.02) 相关。这些发现表明，MDR1 中的 C3435T 和 G2677T/A SNP 与胎盘 P-gp 蛋白表达降低显着相关，而 C1236T 和 C3245T 纯合变异体与其外排活性增加显着相关。
The ABC transporter P-glycoprotein is a product of the MDR1 gene and its function in human placenta is to extrude xenobiotics from the tissue thus decreasing fetal exposure. The goal of this investigation was to examine the effect of three polymorphisms in the MDR1 gene on the expression and activity of placental P-gp. In 199 term placentas examined, the C1236T variant was associated with 11% lower P-gp protein expression than wild type, while the C3435T and G2677T/A variants each were associated with a 16% reduction (p < 0.05). Homozygotes for the C1236T and C3435T variant allele (TT) were associated with 42% and 47% increase in placental P-gp transport activity, respectively (p = 0.04 and p = 0.02) of the prototypic substrate, [3H]-paclitaxel. These findings indicate that the C3435T and G2677T/A SNPs in MDR1 are significantly associated with decreased placental P-gp protein expression, while the C1236T and C3245T homozygous variants are significantly associated with an increase in its efflux activity.
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DOI：
10.1111/j.1742-7843.2008.00351.x
发表时间：
2009-02-01
影响因子：
3.1
作者：
Green, Henrik;Soderkvist, Peter;Peterson, Curt
通讯作者：
Peterson, Curt
DOI：
10.1073/pnas.050585397
发表时间：
2000-03-28
影响因子：
11.1
作者：
Hoffmeyer, S;Burk, O;Brinkmann, U
通讯作者：
Brinkmann, U
影响因子：
15.9
作者：
AWASTHI, S;SINGHAL, SS;AWASTHI, YC
通讯作者：
AWASTHI, YC
DOI：
10.1097/00008571-200405000-00006
发表时间：
2004-05-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Hitzl, M;Schaeffeler, E;Schwab, M
通讯作者：
Schwab, M
影响因子：
5.8
作者：
Wang, Xiao-dan;Meng, Min-xin;Zeng, Su
通讯作者：
Zeng, Su