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.
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