Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and …
S Hoffmeyer, O Burk, O Von Richter… - Proceedings of the …, 2000 - National Acad Sciences
S Hoffmeyer, O Burk, O Von Richter, HP Arnold, J Brockmöller, A Johne, I Cascorbi, T Gerloff…
Proceedings of the National Academy of Sciences, 2000•National Acad SciencesTo 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 …
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 …
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.
National Acad Sciences