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Figure 2 | Genome Medicine

Figure 2

From: Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1

Figure 2

SLCO genetic variants affect expression of hepatic OATPs. (a, b) Pairwise linkage disequilibrium map of the SLCO1B3-SLCO1B1 genomic region (a) and the SLCO2B1 gene (b) including all variants detected in the 143 livers. Coloring corresponds to the standard Haploview (D'/LOD) [31]. (c,d) SLCO1B1 haplotypes, calculated based on the four missense variants present in the liver cohort (c.388A > G, c.463C > A, c.521T > C, c.1929A > C) and also previously described as key variants [8, 80], affect OATP1B1 protein expression in the non-cholestatic liver samples (n = 117). Only haplotypes with frequencies ≥ 2% are given. The effect sizes indicate differences of OATP1B1 expression compared to reference haplotype SLCO1B1*1a. Boldface: significant P-values. (d) SLCO1B1 genotypes (percentage genotype frequencies in brackets) are sorted by median OATP1B1 protein expression. SLCO1B1 alleles harboring only variant c.388A > G and not c.521T > C (*1b, *14, *35, boldface) confer considerably higher OATP1B1 expression in a gene-dose dependent manner. Horizontal line indicates median; boxes indicate the 25th to 75th percentiles; whiskers indicate non-outlier range. (e) Percentage of interindividual variability of expression of OATPs in the non-cholestatic liver samples apportioned to non-genetic factors (gray), regulatory factors (blue), and SLCO variants (orange), and to the combination of all three categories (red) was calculated using multivariate linear regression analyses and stepwise model selection.

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