Amy agena pa3/11/2023 ![]() ![]() These materials cover some of the more commonly tested genes and alleles included in commercially available reagents and platforms, but no characterized RMs are currently available for most genes and alleles included in the more comprehensive assays, particularly for low-frequency variants or variants more commonly found in non-European populations. Although clinical laboratories commonly offer pharmacogenetic tests, and many pharmacogenetic assays are being used for drug development and clinical trials, there are a limited number of quality control and other RMs that have been characterized using multiple methods. 3, 4, 5, 6, 7, 8, 9 Genetic testing laboratories often use genomic DNA samples, from cell lines or residual deidentified patient material, as RMs. ![]() 2Ĭlinical genetic testing laboratories are required by regulations and guided by professional or best practice standards to use reference materials (RMs) for assay development and validation, quality control, and proficiency testing. 1 Pharmacogenetic tests are also used by researchers and pharmaceutical companies for discovery, drug development, and clinical trials. The US Food and Drug Administration (FDA) requires that information about applicable pharmacogenetic tests be included in the labeling of certain FDA-approved drugs, including clopidogrel, warfarin, and abacavir. The boxed warning on clopidogrel (, last accessed September 12, 2014) notes that testing is available to determine the CYP2C19 genotype. Individuals with loss-of-function CYP2C19 variants are not able to effectively metabolize clopidogrel and are at increased risk for adverse cardiovascular events, especially after receiving coronary artery stents. This drug is metabolized to its active form by several cytochrome P (CYP) 450 enzymes, most notably CYP2C19. For example, clopidogrel (Plavix) is a platelet inhibitor that is prescribed to patients with acute coronary syndromes to prevent blood clots. These tests are used clinically to assist development of therapeutic strategies. Pharmacogenetic tests are used to predict or explain an individual's reaction to drugs by assaying for the presence or absence of known genetic polymorphisms in genes encoding drug metabolizing enzymes, drug transporters, drug receptors, or targets of drug action. These publicly available samples will help ensure the accuracy of pharmacogenetic testing. Genotyping results were consistent among laboratories, with most differences in allele assignments attributed to assay design and variability in reported allele nomenclature, particularly for CYP2D6, UGT1A1, and VKORC1. These samples are also being characterized by other pharmacogenetic assays, including next-generation sequencing, which will be reported separately. Through consensus verification, we confirmed the presence of at least 108 variant pharmacogenetic alleles. DNA samples were coded and distributed to volunteer testing laboratories for targeted genotyping using a number of commercially available and laboratory developed tests. One hundred thirty-seven Coriell cell lines were selected based on ethnic diversity and partial genotype characterization from earlier testing. To address this need, the Centers for Disease Control and Prevention–based Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, has characterized 137 genomic DNA samples for 28 genes commonly genotyped by pharmacogenetic testing assays ( CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP4F2, DPYD, GSTM1, GSTP1, GSTT1, NAT1, NAT2, SLC15A2, SLC22A2, SLCO1B1, SLCO2B1, TPMT, UGT1A1, UGT2B7, UGT2B15, UGT2B17, and VKORC1). However, only a limited number of quality control and other reference materials are currently available to support clinical testing. Pharmacogenetic testing is increasingly available from clinical laboratories. ![]()
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