Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.
Article Details
- CitationCopy to clipboard
Marez D, Legrand M, Sabbagh N, Lo Guidice JM, Spire C, Lafitte JJ, Meyer UA, Broly F
Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.
Pharmacogenetics. 1997 Jun;7(3):193-202.
- PubMed ID
- 9241659 [ View in PubMed]
- Abstract
The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various drugs of wide therapeutic use and is a presumed susceptibility factor for certain environmentally-induced diseases. Our aim was to define the mutations and alleles of the CYP2D6 gene and to evaluate their frequencies in the European population. Using polymerase chain reaction-single strand conformation polymorphism analysis, 672 unrelated subjects were screened for mutations in the 9 exons of the gene and their exon-intron boundaries. A total of 48 point mutations were identified, of which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented 52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the 2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor metabolizer subgroup. Fifty-three different alleles were characterized from the mutation pattern and by allele-specific sequencing. They are derived from three major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account for about 87% of all alleles, while the remaining alleles occur with a frequency of 0.1%-2.7%. These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID Cytochrome P450 2D6 P10635 Details - Pharmaco-genomics
Drug Interacting Gene/Enzyme Allele name Genotypes Defining change(s) Type(s) Description Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*3 Not Available - C allele (rs35742686)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*6 Not Available - 1707delT (rs5030655)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*19 Not Available - 2539_2542delAACT (rs72549353)
Effect Inferred Poor drug metabolizer, increased side effects. Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*31 Not Available - -1770G>A
- -1584C>G
- -1235A>G
Effect Inferred Poor drug metabolizer, increased side effects. Details