How and why to screen for CYP2D6 interindividual variability in patients under pharmacological treatments

Manuela De Gregori, Massimo Allegri, Simona De Gregori, Giulia Garbin, Carmine Tinelli, Mario Regazzi, Stefano Govoni, Guglielmina Nadia Ranzani

Research output: Contribution to journalArticle

Abstract

Cytochromes P450 are members of a superfamily of hemoproteins that catalyze a variety of oxidative reactions in the metabolism of endogenous and exogenous hydrophobic substrates. Fifty-eight cytochrome P450 (CYP) isoenzymes belonging to 18 families have been identified in human cells; the corresponding genes are highly polymorphic, and genetic variability underlies interindividual differences in drug response. The polymorphisms of CYP2D6 significantly affect the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates. The number of functional CYP2D6 alleles per genome determines the existence of four different phenotypes, i.e. poor, intermediate, extensive, and ultrarapid metabolizers. CYP2D6 genetic variants include copy number variations, single nucleotide substitutions, frameshift and insertion/deletion mutations. This review reports some of the different methodological approaches used to screen for CYP2D6 variants and focuses on methods that have improved variation detection, from conventional techniques to more recent microarray technology and high throughput DNA sequencing. In addition, this review reports some results on clinical relevance of CYP2D6 polymorphisms and provides examples of variability in drug response associated with interindividual phenotypic differences.

Original languageEnglish
Pages (from-to)276-282
Number of pages7
JournalCurrent Drug Metabolism
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Clinical outcome
  • Customized therapy
  • CYP2D6 polymorphisms
  • Drug metabolism
  • Genotyping techniques
  • Interindividual variability
  • Phenotypes

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

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