Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project.
Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci (CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6. The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci (CYP4F2, EPHX1, ABCB1, HLAB, KIF6, CYP3A4, CYP3A5, TPMT, and DPD) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research.
Pratt
Victoria M
VM
Quest Diagnostics Nichols Institute, Chantilly, Virginia, USA.
Zehnbauer
Barbara
B
Wilson
Jean Amos
JA
Baak
Ruth
R
Babic
Nikolina
N
Bettinotti
Maria
M
Buller
Arlene
A
Butz
Ken
K
Campbell
Matthew
M
Civalier
Chris
C
El-Badry
Abdalla
A
Farkas
Daniel H
DH
Lyon
Elaine
E
Mandal
Saptarshi
S
McKinney
Jason
J
Muralidharan
Kasinathan
K
Noll
LeAnne
L
Sander
Tara
T
Shabbeer
Junaid
J
Smith
Chingying
C
Telatar
Milhan
M
Toji
Lorraine
L
Vairavan
Anand
A
Vance
Carlos
C
Weck
Karen E
KE
Wu
Alan H B
AH
Yeo
Kiang-Teck J
KT
Zeller
Markus
M
Kalman
Lisa
L
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002460:Cell Line; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005819:Genetic Markers; D015894:Genome, Human; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D057089:Pathology, Molecular / Q000295:instrumentation / Q000379:methods; D010597:Pharmacogenetics / Q000295:instrumentation / Q000379:methods; D064417:Vitamin K Epoxide Reductases; D000099148:UGT1A1 Enzyme
D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6; D004247:DNA; D005819:Genetic Markers; D014453:Glucuronosyltransferase; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D000099148:UGT1A1 Enzyme; C450260:CYP2C9 protein, human; C045793:CYP2C19 protein, human; C578523:VKORC1 protein, human