Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population

Clinical implications

Stephen Bernard, Kathleen A. Neville, Anne T. Nguyen, David A. Flockhart

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

DNA polymorphisms have been identified in the genes encoding a number of the cytochrome P450 (CYP) enzymes, leading to wide interindividual variation in drug clearance. CYP2D6 metabolizes a significant number of clinically used medications, and genetic variants of the CYP2D6 isozyme that result in varying levels of metabolic activity are of clinical importance in some settings. The exact nature of the clinical effect caused by polymorphisms of the gene depends on the drug in question and the specific variant alleles expressed, as individual variants result in differing phenotypes with a range of levels of enzymatic activity. Compromised drug efficacy due to CYP2D6 variation has been documented with a variety of agents, and this review considers a number of examples, including the 5-HT3-receptor antagonists, which are used in oncology supportive care for the prophylaxis of nausea and vomiting. CYP2D6 is involved in the metabolism of all of the most commonly available agents, except granisetron, and their efficacy and side effects may therefore be affected by the CYP2D6 polymorphism. Significant interethnic differences in CYP2D6 allele frequencies have been demonstrated from studies across many countries. However, incidences of polymorphisms in the U.S. population have been challenging to characterize because of the country's wide ethnic diversity. The CYP2D6 polymorphism may become more important as robust clinical tests become widely available and as the use of multiple medications and the attendant risk for drug-drug interactions increases.

Original languageEnglish
Pages (from-to)126-135
Number of pages10
JournalOncologist
Volume11
Issue number2
DOIs
StatePublished - Feb 2006

Fingerprint

Cytochrome P-450 CYP2D6
Genetic Polymorphisms
Population
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Granisetron
Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Drug Interactions
Gene Frequency
Nausea
Isoenzymes
Genes
Vomiting
Alleles
Phenotype
DNA
Incidence

Keywords

  • 5-HT-receptor antagonist antiemetics
  • CYP2D6 polymorphism
  • Genetic variability
  • Hepatic metabolism

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population : Clinical implications. / Bernard, Stephen; Neville, Kathleen A.; Nguyen, Anne T.; Flockhart, David A.

In: Oncologist, Vol. 11, No. 2, 02.2006, p. 126-135.

Research output: Contribution to journalArticle

Bernard, Stephen ; Neville, Kathleen A. ; Nguyen, Anne T. ; Flockhart, David A. / Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population : Clinical implications. In: Oncologist. 2006 ; Vol. 11, No. 2. pp. 126-135.
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