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.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / genetics*
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Clinical Trials as Topic
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Drug Discovery
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Gene Frequency / genetics
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Humans
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Liver-Specific Organic Anion Transporter 1
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Membrane Transport Proteins / genetics*
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Neoplasm Proteins / genetics*
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Organic Anion Transporters / genetics*
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Pharmacogenetics
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Polymorphism, Genetic / genetics*
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Liver-Specific Organic Anion Transporter 1
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Membrane Transport Proteins
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Neoplasm Proteins
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Organic Anion Transporters
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SLCO1B1 protein, human