Background: CYP2D6 is one of the most significant polymorphic genes of drugmetabolizing
enzymes due to its association with different metabolic activities and the pharmacokinetics
of CYP2D6 substrates.
Objective: The objective of this study was to explore for a novel haplotype of CYP2D6 in the Japanese
population by using a large database of previous clinical studies.
Methods: We analyzed CYP2D6 genotype data from a total of 723 Japanese individuals for 8 loci
(100C>T, 1758G>A, 1846G>A, 2573 insertion of C, 2850C>T, 2988G>A, 4125 insertion of 9bp, and
4180G>C) and gene deletion. Genotypes were determined by the designated alleles CYP2D6*2, *4,
*5, *10, *14A, *14B, *18, *21, and *41.
Results: The frequencies of the common major haplotypes CYP2D6*1, *10, and *2 in the Japanese
population were respectively 43.5%, 38.0%, and 11.3%. In 11 subjects, diplotypes of CYP2D6 were
not identified and the genotypes at the 8 loci suggested that there were 2 minor haplotypes, one with
only a variation at 4180G>C compared with the wild type CYP2D6*1 (Hap1, frequency: 0.4%) and
one with only a variation at 100C>T (Hap2, frequency: 0.4%). The Hap1 haplotype is considered to
have no effect on metabolic activity, while it is estimated that the Hap2 haplotype does have an effect
on metabolic activity. By comparing with the allele nomenclature for CYP2D6, the Hap2 haplotype
was considered to be a potentially novel haplotype involving 100C>T without 4180G>C.
Conclusion: Using a large database of CYP2D6 genotypes in the Japanese population, we found a
novel haplotype which involves 100C>T without 4180G>C. Although the haplotype will need to be
confirmed by full sequencing, it may be a unique haplotype with an exception to the strong linkage
disequilibrium between 100C>T and 4180G>C.