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Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
Open accessAbstract
To evaluate whether alterations in the multidrug-resistance (MDR)-1 gene correlate with intestinal MDR-1 expression and uptake of orally administered P-glycoprotein (PGP) substrates, we analyzed the MDR-1 sequence in 21 volunteers whose PGP expression and function in the duodenum had been determined by Western blots and quantitative immunohistology ( n = 21) or by plasma concentrations after orally administered digoxin ( n = 8 + 14). We observed a significant correlation of a polymorphism in exon 26 (C3435T) of MDR-1 with expression levels and function of MDR-1. Individuals homozygous for this polymorphism had significantly lower duodenal MDR-1 expression and the highest digoxin plasma levels. Homozygosity for this variant was observed in 24% of our sample population ( n = 188). This polymorphism is expected to affect the absorption and tissue concentrations of numerous other substrates of MDR-1.
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Metadata
- Authors
- Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H. P., Brockmöller, J., Johne, A., Cascorbi, I., Gerloff, T., Roots, I., Eichelbaum, M., & Brinkmann, U.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-03-14
- Volume
- 97
- Issue
- 7
- Pages
- 3473-3478
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2054458932
- Cited by
- 2,365
- References
- 0
- FWCI
- 42.13
- Type
- journal article
- Language
- en
- Open access
- green
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