Concordance of DMET plus genotyping results with those of orthogonal genotyping methods. Clin Pharmacol Ther 2012 Sep;92(3):360-5
Date
08/09/2012Pubmed ID
22871999Pubmed Central ID
PMC3516299DOI
10.1038/clpt.2012.95Scopus ID
2-s2.0-84865431148 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Fernandez CA, Smith C, Yang W, Lorier R, Crews KR, Kornegay N, Hicks JK, Stewart CF, Kawedia JD, Ramsey LB, Liu C, Evans WE, Relling MV, Broeckel UAuthor
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cytochrome P-450 Enzyme SystemFemale
Genes
Genotype
Genotyping Techniques
Humans
Inactivation, Metabolic
Male
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
