A new variant CYP2D6 allele (CYP2D6*21) with a single base insertion in exon 5 in a Japanese population associated with a poor metabolizer phenotype.
Article Details
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Chida M, Yokoi T, Nemoto N, Inaba M, Kinoshita M, Kamataki T
A new variant CYP2D6 allele (CYP2D6*21) with a single base insertion in exon 5 in a Japanese population associated with a poor metabolizer phenotype.
Pharmacogenetics. 1999 Jun;9(3):287-93.
- PubMed ID
- 10471060 [ View in PubMed]
- Abstract
Two poor metabolizer individuals of debrisoquine were identified among 215 healthy Japanese by a phenotyping test. Analysis of the CYP2D6 gene from one of two poor metabolizers, who was not homozygous for the previously described CYP2D6 variant alleles (CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*18), showed that this individual was heterozygous for a new allele, CYP2D6/C8 (CYP2D6*21). CYP2D6*21 had a single cytosine insertion at position 2661 in exon 5. This cytosine insertion generated a stop codon at the 17 bp downstream of this insertion site. A method to detect this allele was established with an allele specific-polymerase chain reaction. This method showed that another one of two poor metabolizers also possessed CYP2D6*21 allele heterozygously. In 318 healthy Japanese, five individuals carried this allele, heterozygously (0.81%, 5/636 chromosomes). Based on the present and our previous data, the poor metabolizer frequency in Japanese was estimated to be 0.39%, which accounted for approximately 45% of the individuals phenotyped as poor metabolizers by in-vivo tests.
DrugBank Data that Cites this Article
- 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*21 Not Available - 2573insC
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*21 Not Available - 2573insC
Effect Inferred Poor drug metabolizer, increased side effects. Details