Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3: Genetic variability and haplotype analysis in white Canadians.
Journal - Drug metabolism and pharmacokinetics
Organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3, are human hepatocyte transporters that mediate the uptake of various endogenous and exogenous substances. Genetic variations in solute carrier transporter (SLCO) 1B1 and SLCO1B3 genes, which encode OATP1B1 and OATP1B3 proteins, could affect the pharmacokinetics of drugs leading to interindividual differences in drug responses. The full extent of SLCO1B1 and SLCO1B3 polymorphisms in white Canadians was analyzed using DNA sequencing procedures. We identified 49 and 41 nucleotide sequence variants leading to 10 and 9 major haplotypes in SLCO1B1 and SLCO1B3 genes, respectively. We report several novel mutations within regulatory and coding regions that could affect genes transcription, translation and function. Comparison with other studies revealed that the distribution of SLCO1B1 and SLCO1B3 polymorphisms and haplotypes differs widely across populations. Data from this survey will ultimately contribute to the design of pharmacogenetic studies in the Canadian population.