Table 2

Polymorphisms in phenotyped individuals; correlation with MDR-1 expression

MDR-1 position, exonType of polymorphismWild type (−)112 1113 D113 F113 K113 P112 2112 4112 5112 8113 A113 C113 E113 G113 N113 O112 3112 6112 7113 I113 L113 M
1/12Exon, 5′ noncodingTT/CT/CT/CT/C
2/−1Exon, TL initiationGG/AG/A
2/61Exon, Asn-AspAA/GA/GA/GA/G
5/307cDNA, Phe-LeuTT/CT/C
11/1199cDNA, Ser-AsnGG/A
12/1236cDNA, wobbleCC/TC/TT/TC/TT/TC/TC/TC/TC/TC/TC/TT/T
26/3396cDNA, wobbleCC/T
26/3435cDNA, wobbleCT/TC/TC/C
PGP expression (OD)2115682142176 40 5291052143082898124615957811451972365115011085541817 2658
PGP expression, mean (N = 21)6279561275
PGP expression, %1521817237731005837962295742680772168100
PGP expression, %, mean (N = 21)254862
Rifampin induction digoxin (AUC), mean (N = 8)57.339.928.6
  • The MDR-1 allele distribution in volunteers and patients was determined by direct sequencing of MDR-1 gene fragments. − indicates homozygous wild-type sequences at the defined positions. The MDR-1 phenotype of the 21 samples was determined by Western blot analysis (9). The MDR-1 genotype in exon 26 was determined by DNA sequencing. Because the expression levels for the samples were determined in two distinct Western blot experiments, the absolute OD values for one set can differ from the values for the other set because of time differences during the exposition to the x-ray film. Therefore in each set the highest expression level was equated to 100% and, beside the densitometric OD values for the MDR-1 expression, the percentage of the expression is also listed. The correlation of the exon 26 SNP with MDR-1 expression and activity after rifampin induction was analyzed in eight volunteers of this group.