{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T23:31:07Z","timestamp":1740180667124,"version":"3.37.3"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient\u2019s genes play a significant role in their response to a drug. Pharmacogenomics aims to optimize drug choice and dose for individual patients by characterizing patients\u2019 pharmacologically relevant genes to identify variants of known impact.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>DNA was extracted from randomly selected remnant whole blood samples from Caucasian patients with previously performed complete blood counts. Samples were genotyped by mass spectrometry using a customized pharmacogenomics panel. A third-party result interpretation service used genotypic results to predict likely individual responses to frequently prescribed drugs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Complete genotypic and phenotypic calls for all tested Cytochrome P450 isoenzymes and other genes were obtained from 152 DNA samples. Of these 152 unique genomic DNA samples, 140 had genetic variants suggesting dose adjustment for at least one drug. Cardiovascular and psychiatry drugs had the highest number of recommendations, which included United States Food and Drug Administration warnings for highly prescribed drugs metabolized by CYP2C19, CYP2C9, CYP2D6, HLA-A, and VKORC1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Risk for each drug:gene pairing primarily depends upon the degree of predicted enzyme impairment or activation, width of the therapeutic window, and whether parent compound or metabolite is pharmacologically active. The resulting metabolic variations range from risk of toxicity to therapeutic failure. Pharmacogenomic profiling likely reduces ADR potential by allowing up front drug\/dose selection to fit a patient\u2019s unique drug-response profile.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jalm\/jfac091","type":"journal-article","created":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T03:30:24Z","timestamp":1673148624000},"page":"251-263","source":"Crossref","is-referenced-by-count":0,"title":["Potential Impact of Pharmacogenomic Single Nucleotide Variants in a Rural Caucasian Population"],"prefix":"10.1093","volume":"8","author":[{"given":"Grace R","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Pathology, Virginia Commonwealth University Health System , Richmond, VA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J","family":"Tsongalis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, NH , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lionel D","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Geisel School of Medicine at Dartmouth and Dartmouth-Hitchcock Medical Center , Lebanon, NH , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael E","family":"Barney","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, NH , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne J","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, NH , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-4189","authenticated-orcid":false,"given":"K","family":"Aaron Geno","sequence":"additional","affiliation":[{"name":"Department of Pathology, Texas Tech University Health Sciences Center El Paso , El Paso, TX , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D","family":"Nerenz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center , Lebanon, NH , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"2023050412164360000_jfac091-B1","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1056\/NEJMra1010600","article-title":"Genomics and drug response","volume":"12","author":"Wang","year":"2011","journal-title":"N Engl J Med"},{"key":"2023050412164360000_jfac091-B2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ymeth.2016.07.023","article-title":"Improving drug safety: from adverse drug reaction knowledge discovery to clinical implementation","volume":"110","author":"Tan","year":"2016","journal-title":"Methods"},{"author":"US Food and Drug Administration","key":"2023050412164360000_jfac091-B3"},{"key":"2023050412164360000_jfac091-B4","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.gene.2019.144050","article-title":"Pharmacogenes (PGx-genes): current understanding and future directions","volume":"718","author":"Katara","year":"2019","journal-title":"Gene"},{"key":"2023050412164360000_jfac091-B5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacol Ther"},{"author":"Pharmacogene Variation Consortium","key":"2023050412164360000_jfac091-B6"},{"author":"PharmGKB","key":"2023050412164360000_jfac091-B7"},{"key":"2023050412164360000_jfac091-B8","doi-asserted-by":"crossref","first-page":"785","DOI":"10.2217\/pgs-2019-0192","article-title":"PARC report: a health-systems focus on reimbursement and patient access to pharmacogenomics testing","volume":"21","author":"Rogers","year":"2020","journal-title":"Pharmacogenomics"},{"key":"2023050412164360000_jfac091-B9","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1038\/s41436-021-01269-9","article-title":"IGNITE Network Pharmacogenetics Working Group. Multi-site investigation of strategies for the clinical implementation of preemptive pharmacogenetic testing","volume":"23","author":"Duarte","year":"2021","journal-title":"Genet Med"},{"key":"2023050412164360000_jfac091-B10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41398-021-01600-7","article-title":"Barriers to clinical adoption of pharmacogenomic testing in psychiatry: a critical analysis","volume":"11","author":"Virelli","year":"2021","journal-title":"Transl Psychiatry"},{"key":"2023050412164360000_jfac091-B11","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/cpt.2526","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 update","volume":"112","author":"Lee","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"2023050412164360000_jfac091-B12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/jalm\/jfaa018","article-title":"Clinical validation of a 106-SNV MALDI-ToF MS pharmacogenomic panel","volume":"5","author":"Williams","year":"2020","journal-title":"J Appl Lab Med"},{"key":"2023050412164360000_jfac091-B13","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2217\/PME.15.10","article-title":"Clinician perspectives on using pharmacogenomics in clinical practice","volume":"12","author":"Unertl","year":"2015","journal-title":"Per Med"},{"key":"2023050412164360000_jfac091-B14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5688\/ajpe75351","article-title":"Assessment of the pharmacogenomics educational needs of pharmacists","volume":"75","author":"McCullough","year":"2011","journal-title":"Am J Pharm Educ"},{"key":"2023050412164360000_jfac091-B15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.japh.2019.03.005","article-title":"Community pharmacists\u2019 educational needs for implementing clinical pharmacogenomic services","volume":"59","author":"Berenbrok","year":"2019","journal-title":"J Am Pharm Assoc"},{"key":"2023050412164360000_jfac091-B16","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cpt.113","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing","volume":"98","author":"Birdwell","year":"2015","journal-title":"Clin Pharmacol Ther"},{"author":"CPIC","key":"2023050412164360000_jfac091-B17"},{"author":"CPIC","key":"2023050412164360000_jfac091-B18"},{"author":"PharmGKB","key":"2023050412164360000_jfac091-B19"},{"key":"2023050412164360000_jfac091-B20","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/clpt.2013.254","article-title":"Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update","volume":"95","author":"Crews","year":"2014","journal-title":"Clin Pharmacol Ther"},{"key":"2023050412164360000_jfac091-B21","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/cpt.1477","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2B6 and efavirenz-containing antiretroviral therapy","volume":"106","author":"Desta","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"2023050412164360000_jfac091-B22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/cpt.1830","article-title":"Clinical Pharmacogenetics Implementation Consortium guideline (CPIC) for CYP2C9 and nonsteroidal anti-inflammatory drugs","volume":"108","author":"Theken","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"2023050412164360000_jfac091-B23","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/cpt.690","article-title":"Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects","volume":"102","author":"Zhou","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"2023050412164360000_jfac091-B24","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1101\/gr.9.8.677","article-title":"dbSNP\u2014Database for single nucleotide polymorphisms and other classes of minor genetic variation","volume":"9","author":"Sherry","year":"1999","journal-title":"Genome Res"},{"key":"2023050412164360000_jfac091-B25"},{"key":"2023050412164360000_jfac091-B26","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/clpt.2011.132","article-title":"Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy (CYP2C19)","volume":"90","author":"Scott","year":"2011","journal-title":"Clin Pharmacol Ther"},{"author":"Fedder","key":"2023050412164360000_jfac091-B27"},{"author":"United States Food and Drug Administration. 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