Preemptive Pharmacogenomic Testing for Precision Medicine: A Comprehensive Analysis of Five Actionable Pharmacogenomic Genes Using Next-Generation DNA Sequencing and a Customized CYP2D6 Genotyping Cascade

Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project...

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Published in:The Journal of molecular diagnostics : JMD Vol. 18; no. 3; p. 438
Main Authors: Ji, Yuan, Skierka, Jennifer M, Blommel, Joseph H, Moore, Brenda E, VanCuyk, Douglas L, Bruflat, Jamie K, Peterson, Lisa M, Veldhuizen, Tamra L, Fadra, Numrah, Peterson, Sandra E, Lagerstedt, Susan A, Train, Laura J, Baudhuin, Linnea M, Klee, Eric W, Ferber, Matthew J, Bielinski, Suzette J, Caraballo, Pedro J, Weinshilboum, Richard M, Black, 3rd, John L
Format: Journal Article
Language:English
Published: United States 01.05.2016
Subjects:
Alleles
Cytochrome P-450 CYP2C19 - genetics
Cytochrome P-450 CYP2C19 - metabolism
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P-450 CYP2D6 - metabolism
Enzyme Activation
Gene Duplication
Genotype
High-Throughput Nucleotide Sequencing
Humans
Pharmacogenetics - methods
Phenotype
Precision Medicine - methods
ISSN:1943-7811, 1943-7811
Online Access:Get more information
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Summary:Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project for the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment Protocol, was designed to evaluate the impact of preemptive PGx and to optimize the workflow in the clinic setting. We used an 84-gene next-generation sequencing panel that included SLCO1B1, CYP2C19, CYP2C9, and VKORC1 together with a custom-designed CYP2D6 testing cascade to genotype the 1013 subjects in laboratories approved by the Clinical Laboratory Improvement Act. Actionable PGx variants were placed in patient's electronic medical records where integrated clinical decision support rules alert providers when a relevant medication is ordered. The fraction of this cohort carrying actionable PGx variant(s) in individual genes ranged from 30% (SLCO1B1) to 79% (CYP2D6). When considering all five genes together, 99% of the subjects carried an actionable PGx variant(s) in at least one gene. Our study provides evidence in favor of preemptive PGx testing by identifying the risk of a variant being present in the population we studied.
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ISSN:1943-7811
1943-7811
DOI:10.1016/j.jmoldx.2016.01.003