51
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.

      Proceedings of the National Academy of Sciences of the United States of America
      Adult, Alleles, Base Sequence, DNA, Exons, Humans, Intestines, metabolism, Male, P-Glycoprotein, genetics, Polymorphism, Genetic, Sequence Homology, Nucleic Acid

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Journal
          10716719
          16264
          10.1073/pnas.050585397

          Chemistry
          Adult,Alleles,Base Sequence,DNA,Exons,Humans,Intestines,metabolism,Male,P-Glycoprotein,genetics,Polymorphism, Genetic,Sequence Homology, Nucleic Acid

          Comments

          Comment on this article