Sequence-based analysis of the CYP2D6*36-CYP2D6*10 tandem-type arrangement, a major CYP2D6*10 haplotype in the Japanese population.
The frequency of the CYP2D6*10 allele (100C>T) in the Japanese is relatively high (0.3-0.4), and the two *10-related genes, Ch1 (currently *10B) and Ch2 (*36), and their tandem arrangement Ch(2)-Ch(1) (*36-*10B) have been reported. Although the tandem form of *36-*10 is assumed to be a major form, no detailed information has been reported for its intervening and flanking regions. Thus in this study, the tandem-type *36-*10B and the single-type *10 were analyzed by long-range PCR and sequencing of the subsequent nested PCR products. The sequence of the entire *36-*10 region confirmed the recombination of CYP2D6*10 with CYP2D7P. Also, we found that most of the *10B-harboring haplotypes have the upstream *36 gene and that the majority of the remaining haplotypes are the single-type *10B. Haplotype frequencies of the single-type *10 and *36-*10B were 0.06 and 0.30, respectively, in the subjects analyzed. Additionally, several novel single nucleotide polymorphisms (SNPs) were found in the *36 region and several *36 haplotypes were identified. This sequence information is an important addition to the CYP2D6 sequence data that was obtained by the human genome project.
Soyama
Akiko
A
Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Saito
Yoshiro
Y
Kubo
Takashi
T
Miyajima
Atsuko
A
Ohno
Yasuo
Y
Komamura
Kazuo
K
Ueno
Kazuyuki
K
Kamakura
Shiro
S
Kitakaze
Masafumi
M
Tomoike
Hitonobu
H
Ozawa
Shogo
S
Sawada
Jun-ichi
J
D024509:3' Flanking Region / Q000235:genetics; D024506:5' Flanking Region / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005787:Gene Frequency; D023061:Gene Order; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007564:Japan; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020539:Sequence Analysis, Protein / Q000379:methods*
D007527:Isoenzymes; D019389:Cytochrome P-450 CYP2D6