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

Summary: 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.