title: 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.
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.
authors.affiliation: Division of Pharmacobio-dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Chida
authors.forename: T
authors.initials: T
authors.lastname: Yokoi
authors.forename: N
authors.initials: N
authors.lastname: Nemoto
authors.forename: M
authors.initials: M
authors.lastname: Inaba
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Kamataki
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D010597:Pharmacogenetics; D010641:Phenotype
chemical_list: D004247:DNA; D019389:Cytochrome P-450 CYP2D6