title: Concordance of DMET plus genotyping results with those of orthogonal genotyping methods.
abstract: There are several hurdles to the clinical implementation of pharmacogenetics. One approach is to employ pre-prescription genotyping, involving interrogation of multiple pharmacogenetic variants using a high-throughput platform. We compared the performance of the Drug Metabolizing Enzymes and Transporters (DMET) Plus array (1,931 variants in 225 genes) with that of orthogonal genotyping methods in 220 pediatric patients. A total of 1,692 variants had call rates >98% and were in Hardy-Weinberg equilibrium. Of these, 259 were genotyped by at least one independent method, and a total of 19,942 single-nucleotide polymorphism (SNP)-patient sample pairs were evaluated. The concordance rate was 99.9%, with only 28 genotype discordances observed. For the genes deemed most likely to be clinically relevant (TPMT, CYP2D6, CYP2C19, CYP2C9, VKORC1, DPYD, UGT1A1, and SLCO1B1), a total of 3,799 SNP-patient sample pairs were evaluable and had a concordance rate of 99.96%. We conclude that the DMET Plus array performs well with primary patient samples, with the results in good concordance with those of several lower-throughput genotyping methods.
authors.affiliation: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: R
authors.initials: R
authors.lastname: Lorier
authors.forename: K R
authors.initials: KR
authors.lastname: Crews
authors.forename: N
authors.initials: N
authors.lastname: Kornegay
authors.forename: J K
authors.initials: JK
authors.lastname: Hicks
authors.forename: C F
authors.initials: CF
authors.lastname: Stewart
authors.forename: J D
authors.initials: JD
authors.lastname: Kawedia
authors.forename: L B
authors.initials: LB
authors.lastname: Ramsey
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: M V
authors.initials: MV
authors.lastname: Relling
authors.forename: U
authors.initials: U
authors.lastname: Broeckel
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D003577:Cytochrome P-450 Enzyme System