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Gaedigk, A. et al.

Gaedigk, Gaedigk, Leeder,

CYP2D7 splice variants in human liver and brain: does CYP2D7 encode functional protein?

A CYP2D7 brain-specific protein metabolizing codeine and encoded by an alternate mRNA has recently been described in Indian subjects. To examine its potential presence in other ethnic backgrounds, CYP2D7 and CYP2D6 full-length splice products were analyzed in liver and brain. CYP2D7 splice variant-specific PCR on 13 subjects revealed the previously reported partial intron 6-containing transcript encoding CYP2D7 in both tissues as a minor variant. This transcript is not predicted to encode functional protein as a frame-shift-reverting deletion in CYP2D7 exon 1 (138delT) was not detected in any transcript or in 285 additional genotyped subjects. The g.14408G > C SNP required for functional transcript also was not observed; all transcripts and individuals genotyped as g.14408G/G that causes a premature stop codon in any splice variants that contain the 57bp intron 6 insertion. Therefore, no evidence for functional CYP2D7 transcripts was observed in Asian, Caucasian or African American individuals.[1]

References

CYP2D7 splice variants in human liver and brain: does CYP2D7 encode functional protein? Gaedigk, A., Gaedigk, R., Leeder, J.S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]

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