title: How and why to screen for CYP2D6 interindividual variability in patients under pharmacological treatments.
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.
authors.affiliation: Department of Genetics and Microbiology, University of Pavia, Pavia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: De Gregori
authors.forename: Massimo
authors.initials: M
authors.lastname: Allegri
authors.forename: Simona
authors.initials: S
authors.lastname: De Gregori
authors.forename: Giulia
authors.initials: G
authors.lastname: Garbin
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.forename: Guglielmina Nadia
authors.initials: GN
authors.lastname: Ranzani
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D004364:Pharmaceutical Preparations; D019389:Cytochrome P-450 CYP2D6