Organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3: genetic variability and haplotype analysis in white Canadians.
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 1B1 (SLCO1B1) 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 gene 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.
Boivin
Andrée-Anne
AA
Laboratoire d'Immunogénétique, Centre de Recherche du Centre Hospitalier de l'université de Montréal et Département de Microbiologie et Immunologie de l'université de Montréal, Montreá al, Canada.
Cardinal
Héloïse
H
Barama
Azemi
A
Pichette
Vincent
V
Hébert
Marie-Josée
MJ
Roger
Michel
M
D020121:5' Untranslated Regions / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D027381:Liver-Specific Organic Anion Transporter 1; D016254:Mutagenesis, Insertional / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011792:Quebec / Q000208:ethnology; D017422:Sequence Analysis, DNA; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D044465:White People / Q000235:genetics*
D020121:5' Untranslated Regions; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3