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Fig. 4 | Genome Medicine

Fig. 4

From: Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1

Fig. 4

Comparative analyses of the activity of the different OCT1 alleles using 10 different OCT1 substrates. Shown are the effects of the major OCT1 alleles (a) and the six most common sub-alleles (b). The allele activity was determined with cellular uptake measurements in HEK293 cells overexpressing different OCT1 alleles. The uptake was measured after incubation for 2 min with 10 μM MPP+, 5 μM TEA+, 5 μM ASP+, 1 μM morphine, 5 μM metformin, 10 μM tyramine, or 1 μM monocrotaline, incubation for 1 min with 1 μM debrisoquine or 1 μM O-desmethyltramadol, or for 3 min with 1 μM tropisetron. OCT1-mediated uptake was calculated by subtracting the uptake in HEK293 cells transfected with the empty pcDNA5/FRT vector from the uptake in the cells transfected with the different OCT1 alleles. The results were represented as a percent of the uptake in the cells transfected with the OCT1*1 allele (shown in black). The values for the uptake of morphine and tropisetron by alleles *3, *4, *5, and *6 are from our previously published studies [3] and [5], respectively. The comparison between OCT1*7A and OCT1*7B alleles (b) were made after transient transfection. All the remaining experiments were performed after stable transfection in HEK293 cells. Shown are mean and standard error of the means of three or more independent experiments

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