CYP2D6: novel genomic structures and alleles.

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Kramer WE, Walker DL, O'Kane DJ, Mrazek DA, Fisher PK, Dukek BA, Bruflat JK, Black JL

CYP2D6: novel genomic structures and alleles.

Pharmacogenet Genomics. 2009 Oct;19(10):813-22. doi: 10.1097/FPC.0b013e3283317b95.

PubMed ID
19741566 [ View in PubMed
]
Abstract

OBJECTIVE: CYP2D6 is a polymorphic gene. It has been observed to be deleted, to be duplicated and to undergo recombination events involving the CYP2D7 pseudogene and surrounding sequences. The objective of this study was to discover the genomic structure of CYP2D6 recombinants that interfere with clinical genotyping platforms that are available today. METHODS: Clinical samples containing rare homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals and two different alleles were analyzed by long-range PCR amplification of individual genes, PCR fragment analysis, allele-specific primer extension assay, and DNA sequencing to characterize alleles and genomic structure. RESULTS: Novel alleles, genomic structures, and the DNA sequence of these structures are described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene duplications or multiplications where two alleles were detected, the chromosome containing the duplication or multiplication had identical tandem alleles. CONCLUSION: Several new CYP2D6 alleles and genomic structures are described which will be useful for CYP2D6 genotyping. The findings suggest that the recombination events responsible for CYP2D6 duplications and multiplications are because of mechanisms other than interchromosomal crossover during meiosis.

DrugBank Data that Cites this Article

Pharmaco-genomics
DrugInteracting Gene/EnzymeAllele nameGenotypesDefining change(s)Type(s)DescriptionDetails
MetoprololCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		ADR InferredIncreased risk of slow heart rate (bradycardia)Details
VenlafaxineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirementsDetails
AmitriptylineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
ImipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
DextromethorphanCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirementsDetails
NortriptylineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
TamoxifenCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor response to drug treatment, shorter time to relapseDetails
DesipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
ClomipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
AtomoxetineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …		Effect InferredPoor drug metabolizer, increased side effects.Details