Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: discovery of novel allelic variants.

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Montane Jaime LK, Lalla A, Steimer W, Gaedigk A

Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: discovery of novel allelic variants.

Pharmacogenomics. 2013 Feb;14(3):261-76. doi: 10.2217/pgs.12.207.

PubMed ID
23394389 [ View in PubMed
]
Abstract

BACKGROUND: The highly polymorphic CYP2D6 gene has extensively been studied in many populations, but there is a void of knowledge regarding CYP2D6 pharmacogenetics and activity in populations with unique ancestries and admixture, such as those residing in Trinidad and Tobago. MATERIALS & METHODS: 167 healthy Indo- and 103 Afro-Trinidadians were phenotyped with dextromethorphan and extensively genotyped. Gene resequencing was performed to resolve cases with genotype/phenotype discordance. RESULTS: CYP2D6 activity did not differ between the Indo-Trinidadians and Afro-Trinidadians. Poor metabolizers were, however, more frequent in the Indo-Trinidadians (4.19 vs 1.94%), and unique allele frequency patterns were observed. Two novel nonfunctional allelic variants were found among the Indo-Trinidadians in two discordant cases. CYP2D6*100 is characterized by a single nucleotide deletion and CYP2D6*101 by a 19-bp deletion; both cause frameshifts. CONCLUSION: Our study underscores the importance of thoroughly characterizing the genetic make up of unique populations when considering pharmacogenetic testing for individualized therapy.

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*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		ADR InferredIncreased risk of slow heart rate (bradycardia)Details
MetoprololCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		ADR InferredIncreased risk of slow heart rate (bradycardia)Details
VenlafaxineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
VenlafaxineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirementsDetails
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirementsDetails
AmitriptylineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
AmitriptylineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
ImipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
ImipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
DextromethorphanCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirementsDetails
DextromethorphanCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirementsDetails
NortriptylineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
NortriptylineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
TamoxifenCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor response to drug treatment, shorter time to relapseDetails
TamoxifenCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor response to drug treatment, shorter time to relapseDetails
DesipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
DesipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
ClomipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
ClomipramineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
AtomoxetineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …		Effect InferredPoor drug metabolizer, increased side effects.Details
AtomoxetineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635		CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …		Effect InferredPoor drug metabolizer, increased side effects.Details