title: International Transporter Consortium commentary on clinically important transporter polymorphisms.
abstract: This Commentary focuses on genetic polymorphisms in membrane transporters. We present two polymorphisms for which there is a compelling body of literature supporting their clinical relevance: OATP1B1 (c.521T>C, p.V174A, rs4149056) and BCRP (c.421C>A, p.Q141K, rs2231142). The clinical evidence demonstrating their role in variation in pharmacokinetics and pharmacodynamics is described along with their allele frequencies in ethnic populations. Recommendations for incorporating studies of transporter polymorphisms in drug development are provided, along with the regulatory implications.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. kathy.giacomini@ucsf.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Giacomini
authors.forename: P V
authors.initials: PV
authors.lastname: Balimane
authors.forename: S K
authors.initials: SK
authors.lastname: Cho
authors.forename: M
authors.initials: M
authors.lastname: Eadon
authors.forename: T
authors.initials: T
authors.lastname: Edeki
authors.forename: K M
authors.initials: KM
authors.lastname: Hillgren
authors.forename: S-M
authors.initials: SM
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: D
authors.initials: D
authors.lastname: Weitz
authors.forename: Y
authors.initials: Y
authors.lastname: Wen
authors.forename: C Q
authors.initials: CQ
authors.lastname: Xia
authors.forename: S W
authors.initials: SW
authors.lastname: Yee
authors.forename: H
authors.initials: H
authors.lastname: Zimdahl
authors.forename: M
authors.initials: M
authors.lastname: Niemi
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human