CYP2D7 Sequence Variation Interferes with TaqMan CYP2D6 (*) 15 and (*) 35 Genotyping

Frontiers in Pharmacology
Amanda K RiffelAndrea Gaedigk

Abstract

TaqMan™ genotyping assays are widely used to genotype CYP2D6, which encodes a major drug metabolizing enzyme. Assay design for CYP2D6 can be challenging owing to the presence of two pseudogenes, CYP2D7 and CYP2D8, structural and copy number variation and numerous single nucleotide polymorphisms (SNPs) some of which reflect the wild-type sequence of the CYP2D7 pseudogene. The aim of this study was to identify the mechanism causing false-positive CYP2D6 (*) 15 calls and remediate those by redesigning and validating alternative TaqMan genotype assays. Among 13,866 DNA samples genotyped by the CompanionDx® lab on the OpenArray platform, 70 samples were identified as heterozygotes for 137Tins, the key SNP of CYP2D6 (*) 15. However, only 15 samples were confirmed when tested with the Luminex xTAG CYP2D6 Kit and sequencing of CYP2D6-specific long range (XL)-PCR products. Genotype and gene resequencing of CYP2D6 and CYP2D7-specific XL-PCR products revealed a CC>GT dinucleotide SNP in exon 1 of CYP2D7 that reverts the sequence to CYP2D6 and allows a TaqMan assay PCR primer to bind. Because CYP2D7 also carries a Tins, a false-positive mutation signal is generated. This CYP2D7 SNP was also responsible for generating false-positive signals...Continue Reading

References

Jul 4, 2001·Genome Research·K RanadeD Botstein
Nov 18, 2003·Naunyn-Schmiedeberg's Archives of Pharmacology·Ulrich M ZangerMichel Eichelbaum
Jan 30, 2007·Clinical Pharmacology and Therapeutics·A GaedigkJ Steven Leeder
Nov 1, 2007·Clinical Pharmacology and Therapeutics·A GaedigkJ S Leeder
Nov 16, 2007·Pharmacology & Therapeutics·Magnus Ingelman-SundbergCristina Rodriguez-Antona
Aug 13, 2008·Analytical and Bioanalytical Chemistry·Ulrich M ZangerMatthias Schwab
Sep 19, 2009·Pharmacogenomics·Fabiana B KohlrauschMara H Hutz
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 12, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
May 25, 2010·Biochemical and Biophysical Research Communications·Magnus Ingelman-Sundberg, Sarah C Sim
Dec 22, 2011·Drug Metabolism and Pharmacokinetics·Lay Kek Teh, Leif Bertilsson
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Mar 15, 2013·Clinical Pharmacology and Therapeutics·J K HicksUNKNOWN Clinical Pharmacogenetics Implementation Consortium
Apr 5, 2013·PloS One·Anastasia FedickNathan R Treff
Oct 4, 2013·Pharmacogenomics·Gregorio Antonio Alcazar-GonzálezHugo Alberto Barrera-Saldaña
Oct 25, 2013·International Review of Psychiatry·Andrea Gaedigk
Jan 25, 2014·Clinical Pharmacology and Therapeutics·K R CrewsUNKNOWN Clinical Pharmacogenetics Implementation Consortium
Oct 9, 2014·Annual Review of Pharmacology and Toxicology·Henry M DunnenbergerMary V Relling
Mar 20, 2015·Scientific Reports·Andrea GaedigkJ Steven Leeder
May 15, 2015·Clinical Pharmacology and Therapeutics·J K HicksUNKNOWN Clinical Pharmacogenetics Implementation Consortium

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Citations

Sep 24, 2019·Clinical Pharmacology and Therapeutics·Charity NofzigerAndrea Gaedigk
Feb 26, 2021·The Journal of Molecular Diagnostics : JMD·Amy J TurnerAndrea Gaedigk
Oct 18, 2021·The Journal of Molecular Diagnostics : JMD·Robert J SickoDenise M Kay

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Datasets Mentioned

BETA
AY545216
ENS00000205702
ENS00000612115
ENS00000263181
ENS00000278088

Methods Mentioned

BETA
genotyping
PCR
electrophoresis

Software Mentioned

xTAG
ENSEMBL
OpenArray
IS

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