ABCMdb

PMID: 12426521

Siegmund W, Ludwig K, Giessmann T, Dazert P, Schroeder E, Sperker B, Warzok R, Kroemer HK, Cascorbi I
The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol.
Clin Pharmacol Ther. 2002 Nov;72(5):572-83., [PubMed]

Sentences

No. Mutations Sentence Comment

32 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp The following 10 most frequent or putatively functional SNPs of the MDR1 gene were identified, as recently described19 : intron 1 (exon 2 -1) G/A, exon 2 A61G (amino acid exchange Asn21Asp), intron 6 (exon 6 ϩ139) C/T, exon 11 G1199A (Ser400Asn), exon 12 C1236T, intron 12 (exon 12 ϩ44) C/T, intron 16 (exon 17 -76) T/A, exon 21 G2677T (Ala893Ser), G2677A (Ala893Thr), and exon 26 C3435T. Login to comment 97 ABCB1 p.Ser893Ala In fact, substitution of alanine for serine at position 893 of AdrR MCF-7 cells resulted in a different multidrug-resistance pattern.37 In our study both variants in cDNA position 2677 changed neither duodenal MDR1 mRNA expression nor duodenal content of P-glycoprotein. Login to comment 112 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp Other authors, however, did not observe any significant correlation between the MDR1 genotype and fexofenadine disposition35 ; furthermore, a study in human placenta trophoblasts obtained from 100 Japanese women revealed less placental P-glycoprotein (Western blotting) in individuals having the G2677A/T allele.20 The nonanonymous variants A61G (Asn21Asp) in exon 2 and G1199A (Ser400Asn) in exon 11 were also expected to have a functional impact on human P-glycoprotein. Login to comment 113 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp The Asn21Asp exchange is located close to the N-terminus and the Ser400Asn variant just preceding the first adenosine triphosphate-binding domain.22 However, both mutations in our study did not influence P-glycoprotein expression and talinolol disposition. Login to comment