Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?
- Univ. of Cincinnati Medical Center, OH (United States)
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.
- OSTI ID:
- 518504
- Journal Information:
- American Journal of Human Genetics, Vol. 60, Issue 2; Other Information: PBD: Feb 1997
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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