Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events

Clin Pharmacol Ther. 2007 Feb;81(2):242-51. doi: 10.1038/sj.clpt.6100033.


Duplications and multiplications of active CYP2D6 genes can cause ultrarapid drug metabolism and lead to therapeutic failure. Multiple functional and non-functional duplication alleles have been further characterized. Duplications were detected by long-range polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and sequence analysis. A PCR fragment encompassing the entire duplicated gene was utilized for detailed characterization. Duplications occurred at 1.3, 5.75, and 2.0% in Caucasian, African American, and racially mixed populations, respectively (n=887 total). Of those 28, 47, and 17% were non-functional CYP2D6*4 x N. Twelve unique duplication alleles were detected: *1 x N, *2 x N, *4 x N, *6 x N, *10 x N, *17 x N, *17 x N[spacer], *29 x N, *35 x N, *43 x N, *45 x N, and a novel non-functional tandem arrangement of a chimeric 2D7/2D6 and *1 gene. All novel duplications except *35 x N were found in African Americans. Accurate identification of gene duplication events is essential to avoid false-positive ultrarapid metabolism assignments and thus, overestimation of predicted activity and increased risk for unwanted adverse events.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics
  • Alleles
  • Continental Population Groups / classification
  • Continental Population Groups / genetics
  • Cytochrome P-450 CYP2D6 / genetics*
  • European Continental Ancestry Group / genetics
  • Gene Amplification
  • Gene Duplication*
  • Gene Frequency
  • Genetic Heterogeneity*
  • Genotype
  • Humans
  • Models, Genetic
  • Polymerase Chain Reaction
  • Predictive Value of Tests


  • Cytochrome P-450 CYP2D6