A rare insertion of T226 in exon 1 of CYP2D6 causes a frameshift and is associated with the poor metabolizer phenotype: CYP2D6*15

Pharmacogenetics

Volumn 6, Issue 3, 1996, Pages 269-272

  Sachse, Christoph ^a   Brockmöller, Jürgen ^a   Bauer, Steffen ^a   Reum, Torsten ^a   Roots, Ivar ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Debrisoquine polymorphism; Genotyping; Human cytochrome P450 2D6

Indexed keywords

CYTOCHROME P450 ISOENZYME; DEBRISOQUINE; DEXTROMETHORPHAN; DRUG METABOLITE; CYTOCHROME P450 2D6;

ADULT; ALLELE; ARTICLE; CASE REPORT; DRUG METABOLISM; DRUG URINE LEVEL; EXON; GENE INSERTION; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; MALE; MUTANT; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; FRAMESHIFT MUTATION; GENETICS; METABOLISM; PSEUDOGENE; URINE;

ADULT; ALLELES; CYTOCHROME P-450 CYP2D6; DEBRISOQUIN; DEXTROMETHORPHAN; EXONS; FRAMESHIFT MUTATION; HUMANS; MALE; PHENOTYPE; PSEUDOGENES;

EID: 0029661560     PISSN: 0960314X     EISSN: None     Source Type: Journal    
DOI: 10.1097/00008571-199606000-00012     Document Type: Article

References (16)

1. Brockmöller J, Roots I. Assessment of liver metabolic function. Clinical implications. Clin Pharmacokinet 1994: 27, 216-248.
2. Broly F, Meyer UA. Debrisoquine oxidation polymorphism: phenotypic consequences of a 3-base-pair deletion in exon 5 of the CYP2D6 gene. Pharmacogenetics 1993: 3, 123-130.
3. Chan K. Comparison of gas Chromatographic and high-performance liquid Chromatographic assays for the determination of debrisoquine and its 4-hydroxy metabolite in human fluids. J Chromatogr 1988: 425, 311-321.
4. Chen ZR, Somogyi AA, Bochner F. Simultaneous determination of dextromethorphan and three metabolites in plasma and urine using high-performance liquid chromatography with application to their disposition in man. Ther Drug Monit 1990: 12, 97-104.
5. Daly AK, Brockmöller J, Broly F, Eichelbaum M, Evans WE, Gonzalez FJ, Huang J-D, Idle JR, Ingelman-Sundberg M, Ishizaki T, Jacqz-Aigrain E, Meyer UA, Nebert DW, Steen VM, Wolf CR, Zanger UM. Nomenclature for human CYP2D6 alleles. Pharmacogenetics 1996: 6, 193-201.
6. 1795 in exon 3 generates a premature stop codon. Pharmacogenetics 1994a: 4, 271-274.
7. Evert B, Griese EU, Eichelbaum M. A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine. Naunyn Schmiedeberg's Arch Pharmacol 1994b: 350, 434-439.
8. Gaedigk A, Blum M, Gaedigk R, Eichelbaum M, Meyer UA. Deletion of the entire cytochrome P450 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 1991: 48, 943-950.
9. 1934 to A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3′ splice recognition site. Am J Hum Genet 1990: 47, 994-1001.
10. Heim M, Meyer UA. Genotyping of poor metabolizers of debrisoquine by allele-specific PCR amplification. Lancet 1990: 336, 529-532.
11. Kagimoto M, Heim M, Kagimoto K, Zeugin T, Meyer UA. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. J Biol Chem 1990: 265, 17209-17214.
12. Kimura S, Umeno M, Skoda RC, Meyer UA, Gonzalez FJ. The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and isolation of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am J Hum Genet 1989: 45, 889-904.
13. Saxena R, Shaw GL, Relling MV, Frame JN, Moir DT, Evans WE, Caporaso N. Weiffenbach B. Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype. Hum Molec Genet 1994: 3, 923-926.
14. Skoda RC, Gonzalez FJ, Demierre A, Meyer UA. Two mutant alleles of the human cytochrome P-450db1 gene (P450C2D1) associated with genetically deficient metabolism of debrisoquine and other drugs. Proc Natl Acad Sci USA 1988: 85, 5240-5243.
15. Tefre T, Daly AK, Armstrong M, Leathart JBS, Idle JR, Brøgger A, Børresen AL. Genotyping of the CYP2D6 gene in Norwegian lung cancer patients and controls. Pharmacogenetics 1994: 4, 47-57.
16. Tyndale R, Aoyama T, Broly F, Matsunaga T, Inaba T, Kalow W, Gelboin HV, Meyer UA, Gonzalez FJ. Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype. Pharmacogenetics 1991: 1, 26-32.