Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?

Nebert, D W

Title: Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?

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Abstract

The beautiful report by Sachse in this issue of the journal represents the culmination of 2 decades of increasingly exciting work on the {open_quotes}debrisoquine oxidation polymorphism,{close_quotes} one of dozens of pharmacogenetic or ecogenetic polymorphisms that have been shown to have an important impact on innumerable clinical diseases. Pharmacogenetics is the study of the hereditary basis of the differences in responses to drugs. Ecogenetics is the broader field of interindividual differences in response to all environmental chemical and physical agents (e.g., heavy metals, insecticides, compounds formed during combustion, and UV radiation). It is now clear that each of us has his or her own {open_quotes}individual fingerprint{close_quotes} of unique alleles encoding the so-called drug-metabolizing enzymes (DMEs) and the receptors that regulate these enzymes. In this invited editorial, I first introduce the current thinking in the field of DME (and DME-receptor) research and how DMEs have evolved from animal-plant interactions. I then describe the debrisoquine oxidation polymorphism, as well as two other relevant DME polymorphisms; show the relationship between these polymorphisms and human disease; provide examples of synergistic effects caused by the combination of two DME polymorphisms; and discuss the ethical considerations of such research. Last, I speculate on why these allelic frequenciesmore »« less

Authors:

Nebert, D W ^[1]

Univ. of Cincinnati Medical Center, OH (United States)

Publication Date:: Sat Feb 01 00:00:00 EST 1997

OSTI Identifier:: 518504

Resource Type:: Journal Article

Journal Name:: American Journal of Human Genetics

Additional Journal Information:: Journal Volume: 60; Journal Issue: 2; Other Information: PBD: Feb 1997

Country of Publication:: United States

Language:: English

Subject:: 55 BIOLOGY AND MEDICINE, BASIC STUDIES; 56 BIOLOGY AND MEDICINE, APPLIED STUDIES; TOXIC MATERIALS; ENVIRONMENTAL EXPOSURE; ENZYMES; GENE REGULATION; ENZYME ACTIVITY; GENE MUTATIONS; RECEPTORS; CARCINOGENS; TOXICITY; DRUGS; METABOLISM; PHARMACOLOGY; ETHICAL ASPECTS; HUMAN POPULATIONS; PHENOTYPE; NEOPLASMS; DISEASES; THERAPY; CYTOCHROMES

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                    Nebert, D W. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?.  United States: N. p., 1997. 
        Web.

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                    Nebert, D W. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?.  United States.

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                    Nebert, D W. 1997.  
        "Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?".  United States.

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@article{osti_518504,

  title        = {Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?},

  author       = {Nebert, D W},

  abstractNote = {The beautiful report by Sachse in this issue of the journal represents the culmination of 2 decades of increasingly exciting work on the {open_quotes}debrisoquine oxidation polymorphism,{close_quotes} one of dozens of pharmacogenetic or ecogenetic polymorphisms that have been shown to have an important impact on innumerable clinical diseases. Pharmacogenetics is the study of the hereditary basis of the differences in responses to drugs. Ecogenetics is the broader field of interindividual differences in response to all environmental chemical and physical agents (e.g., heavy metals, insecticides, compounds formed during combustion, and UV radiation). It is now clear that each of us has his or her own {open_quotes}individual fingerprint{close_quotes} of unique alleles encoding the so-called drug-metabolizing enzymes (DMEs) and the receptors that regulate these enzymes. In this invited editorial, I first introduce the current thinking in the field of DME (and DME-receptor) research and how DMEs have evolved from animal-plant interactions. I then describe the debrisoquine oxidation polymorphism, as well as two other relevant DME polymorphisms; show the relationship between these polymorphisms and human disease; provide examples of synergistic effects caused by the combination of two DME polymorphisms; and discuss the ethical considerations of such research. Last, I speculate on why these allelic frequencies of the DME genes might exist in human populations in the first place. 35 refs.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/518504},
  journal      = {American Journal of Human Genetics},
number       = 2,

  volume       = 60,

  place        = {United States},

  year         = {Sat Feb 01 00:00:00 EST 1997},

  month        = {Sat Feb 01 00:00:00 EST 1997}

}

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