A silent mutation (2939G>A, exon 6; CYP2D6*59) leading to impaired expression and function of CYP2D6

Pharmacogenetics and Genomics

Volumn 16, Issue 10, 2006, Pages 767-770

  Toscano, Claudia ^a   Raimundo, Sebastian ^a,b   Klein, Kathrin ^a   Eichelbaum, Michel ^a   Schwab, Matthias ^a   Zanger, Ulrich M ^a  

^a DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^b UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

Cytochrome P450 2D6; Intermediate metabolizer; Pharmacogenetics; Single nucleotide polymorphism; Sparteine polymorphism; Synonymous mutation

Indexed keywords

CYTOCHROME P450 2D6; ENZYME; MESSENGER RNA; PROPAFENONE; PROPAFENONE HYDROXYLASE; SPARTEINE; UNCLASSIFIED DRUG;

ALLELE; ARTICLE; CONTROLLED STUDY; DRUG OXIDATION; ENZYME ACTIVITY; EXON; GENE; GENE FREQUENCY; GENE MUTATION; GENE SEQUENCE; GENOTYPE; HAPLOTYPE; HEPATOMA CELL; HUMAN; HUMAN CELL; INTRON; OXIDATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SINGLE NUCLEOTIDE POLYMORPHISM;

BASE SEQUENCE; BLOTTING, WESTERN; CELL LINE, TUMOR; CYTOCHROME P-450 CYP2D6; DNA PRIMERS; EXONS; HAPLOTYPES; HUMANS; MUTATION; PHENOTYPE; RNA, MESSENGER;

EID: 33749024414     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/01.fpc.0000236331.03681.24     Document Type: Article

References (14)

1. Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol 2004; 369:23-37.
2. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005; 5:6-13.
3. Sachse C, Brockmoller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997; 60:284-295.
4. Griese EU, Zanger UM, Brudermanns U, Gaedigk A, Mikus G, Morike K, et al. Assessment of the predictive power of genotypes for the in-vivo catalytic function of CYP2D6 in a German population. Pharmacogenetics 1998; 8:15-26.
5. Raimundo S, Fischer J, Eichelbaum M, Griese EU, Schwab M, Zanger UM. Elucidation of the genetic basis of the common 'intermediate metabolizer' phenotype for drug oxidation by CYP2D6. Pharmacogenetics 2000; 10:577-581.
6. Zanger UM, Fischer J, Raimundo S, Stuven T, Evert BO, Schwab M, et al. Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP2D6. Pharmacogenetics 2001; 11:573-585.
7. Raimundo S, Toscano C, Klein K, Fischer J, Griese EU, Eichelbaum M, et al. A novel intronic mutation, 2988G> A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects. Clin Pharmacol Ther 2004; 76:128-138.
8. Zanger UM, Schwab M, Toscano C, Eichelbaum M. Limited association of the 2988G> A single nucleotide polymorphism with CYP2D6*41 in black subjects: reply to the editor. Clin Pharmacol Ther 2005; 77:230-231.
9. Toscano C, Klein K, Blievernicht J, Schaeffeler E, Saussele T, Raimundo S, et al. Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41 allele caused by the intronic SNP 2988G> A: evidence for modulation of splicing events. Pharmacogenet Genomics 2006 (in Press).
10. Kagimoto M, Heim M, Kagimoto K, Zeugin T, Meyer UA. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. J Biol Chem 1990; 265:17209-17214.
11. Evert B, Eichelbaum M, Haubruck H, Zanger UM. Functional properties of CYP2D6 1 (wild-type) and CYP2D6 7 (His324Pro) expressed by recombinant baculovirus in insect cells. Naunyn Schmiedebergs Arch Pharmacol 1997; 355:309-318.
12. Johansson I, Lundqvist E, Bertilsson L, Dahl ML, Sjoqvist F, Ingelman-Sundberg M. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci U S A 1993; 90:11825-11829.
13. Marez D, Legrand M, Sabbagh N, Guidice JM, Spire C, Lafitte JJ, et al. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics 1997; 7:193-202.
14. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 2003; 31:3406-3415.