Potential Impact of Pharmacogenomic Single Nucleotide Variants in a Rural Caucasian Population. J Appl Lab Med 2023 Mar 06;8(2):251-263
Date
01/08/2023Pubmed ID
36611001Pubmed Central ID
PMC10539040DOI
10.1093/jalm/jfac091Scopus ID
2-s2.0-85150000640 (requires institutional sign-in at Scopus site)Abstract
BACKGROUND: In the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient's 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' pharmacologically relevant genes to identify variants of known impact.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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's unique drug-response profile.
Author List
Williams GR, Tsongalis GJ, Lewis LD, Barney RE, Cook LJ, Aaron Geno K, Nerenz RDAuthor
Robert D. Nerenz PhD Associate Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cytochrome P-450 CYP2D6Drug-Related Side Effects and Adverse Reactions
Genotype
Humans
Nucleotides
Pharmaceutical Preparations
Pharmacogenetics
United States
Vitamin K Epoxide Reductases
