title: Diverse structures of chimeric CYP-REP7/6-containing CYP2D6 and a novel defective CYP2D6 haplotype harboring single-type *36 and CYP-REP7/6 in Japanese.
abstract: Chimeric REP7/6 has been used as a marker of CYP2D6 deletion, such as for CYP2D6*5. However, the CYP2D6*10D (*10D) haplotype found in a Japanese population consist of CYP2D6*10B, CYP2D7P-derived 3'-flanking region, and a chimeric repetitive sequence, CYP-REP7/6 (REP7/6) (Ishiguro et al. Clin. Chim. Acta. 2004: 347, 217-221). From our analysis, REP7/6 was found in 26 out of 254 Japanese subjects. Thus, the REP7/6-containing CYP2D6 genes (2D6-REP7/6) were analyzed in detail. In order to specifically detect the 2D6-REP7/6 structure, primers were designed in CYP2D6 intron 6 and the REP7/6 3'-flanking region. Among 26 subjects analyzed by PCR, 5 had 2D6-REP7/6. The other 21 subjects were confirmed to have *5 by another *5-specific primer set. Three out of five subjects with 2D6-REP7/6 had the *10D structure. However, further analysis by PCR and sequencing revealed that their haplotypes were further divided into tandem-type *36-*10D (n=2) and single-type *10D (n=1). The remaining two subjects had a novel type of a *36-containing defective structure that consists of CYP2D6*36 and 3'-flanking REP7/6 (single-type *36-REP7/6). Then, REP7/6 sequences in *5, *10D, *36-*10D, and single-type *36 were determined and classified into 5 types: types A to D for *5, type E for *10D and *36-*10D, and type F for *36. These findings could be useful for accurate determination of *5 and REP7/6-harboring aberrant CYP2D6 haplotypes.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Kamiyoga, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Soyama
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA; D019389:Cytochrome P-450 CYP2D6