Regulatory Polymorphisms and their Contribution to Interindividual Differences in the Expression of Enzymes Influencing Drug and Toxicant Disposition

The unexpected paucity of human protein encoding genes suggested that polymorphisms altering gene expression might be more important than initially thought. From an evolutionary perspective, traits such as xenobiotic metabolism and transport that require a dynamic response to environmental changes w...

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Bibliographic Details
Published in:Drug metabolism reviews 2008-01, Vol.40 (2), p.263-301
Main Authors: Hines, Ronald N., Koukouritaki, Sevasti B., Poch, Mark T., Stephens, Michael C.
Format: Article
Language:English
Subjects:
Biotransformation - genetics
DNA sequence variants
Drug metabolism
Drug transport
Enzymes - genetics
Enzymes - metabolism
Epoxide Hydrolases - genetics
Gene Expression Regulation, Enzymologic
Gene regulation
Genotype
Humans
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Oxidoreductases - genetics
Pharmaceutical Preparations - metabolism
Phenotype
Polymorphism, Genetic
Promoter
Regulatory polymorphism
Transferases - genetics
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Summary:The unexpected paucity of human protein encoding genes suggested that polymorphisms altering gene expression might be more important than initially thought. From an evolutionary perspective, traits such as xenobiotic metabolism and transport that require a dynamic response to environmental changes would evolve more efficiently through variation in regulatory sequences versus coding variants. Such variation would be manifest as co-dominant traits and selection pressures would operate more efficiently because of their ability to impact fitness in the heterozygous state. Our current understanding of regulatory polymorphisms impacting drug disposition is reviewed including specific discussion regarding knowledge gaps and future research opportunities.
ISSN:0360-2532
1097-9883
DOI:10.1080/03602530801952682