Pattern of SNPs in MDR1,MRP1,and BCRP

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Pattern of SNPs in MDR1,MRP1,and BCRP
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Fig 1Cellular factors that cause drug resistance.
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Fig 2 Structures of ABC transporters known to
confer drug resistance.
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Review for drug transporters pharmacogenetics
MDR1
A neutral marker, but functionally predictive
exon26C3435T
T3435 is correlate with low expression level,
low transport activity, and high plasma
concentration of some drug such as digoxin.
A putatively causative SNP, exon21Ala893Ser is
reported to be associated with
exon26C3435T, but the phenotype of allele
T3435 --- Ser893 is in contrast to the confirmed
one of T3435.
How to reconcile the controversy , is Ala893Ser
the causative SNP?
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Table 1.SNPs distribution of 3 multidrug
resistance transporter genes
Table 2 Indices of population genetics for 3
multidrug resistance transporter genes.
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Updata of Hes lab from Chinese
Downdata of PNAS from Caucasian
Fig 3 In MDR1, some individual SNP are
associated with the reported nonsynonymous maker
C3435T, which can predicts function and phenotype.
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Table 3 Association in MDR1 between the putative
causative SNPs and the functional maker T3435C in
Chinese population.
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Fig 4 Pairwise D' in sliding pairs of SNPs
intervened with 0,1,or 2 SNP respectively (ABCB1).
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Fig 5Observed and expected heterozygosity of
haplotypes in sliding windows of consecutive sets
of 5 SNPs (ABCB1).
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Fig 6 Pairwise LD and physical distance for
SNPs in ABCG2
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Fig 7 Pairwise LD and physical distance for
SNPs in ABCC1
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ABCG2 association between B and C is indicated.
ABCC1 association between B and C is
indicated. Table 4 Pairwise D' for putative
functional SNPs.
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2 implications
As to MDR1 pharmacogenetics, exon21Ala893Ser is
significantly associated with the predictive
marker, exon26C3435T, there is urgent need for
phenotyping in vitro and in vivo to confirm it
function.
As to MRP1 and BCRP, some putatively functional
SNPs are associated, and concerned haplotypes
maybe change the transporters function to a
greater extent.
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Thanks!