Modulation of human placental P-glycoprotein expression and activity by MDR1 gene polymorphisms release_kb665dgqkzgwtfcgscfbdjlr6e

by Sarah J. Hemauer, Tatiana N. Nanovskaya, Sherif Z. Abdel-Rahman, Svetlana L. Patrikeeva, Gary D.V. Hankins, Mahmoud S. Ahmed

Published in Biochemical Pharmacology by Elsevier BV.

2010   Volume 79, Issue 6, p921-925

Abstract

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, [(3)H]-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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Type  article-journal
Stage   published
Date   2009-11-06
Language   en ?
DOI  10.1016/j.bcp.2009.10.026
PubMed  19896927
PMC  PMC2812613
Wikidata  Q33615534
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