1. Blood gene expression profiling of an early acetaminophen response
- Author
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Pierre R. Bushel, Paul B. Watkins, Rickie D. Fannin, Richard S. Paules, and Kevin Gerrish
- Subjects
0301 basic medicine ,Male ,Time Factors ,Pharmacogenomic Variants ,Administration, Oral ,Pharmacology ,Transcriptome ,0302 clinical medicine ,Gene expression ,Gene Regulatory Networks ,Single-Blind Method ,030212 general & internal medicine ,Whole blood ,Oligonucleotide Array Sequence Analysis ,digestive, oral, and skin physiology ,Alanine Transaminase ,Analgesics, Non-Narcotic ,Middle Aged ,Healthy Volunteers ,Molecular Medicine ,Female ,medicine.drug ,Adult ,Adolescent ,Placebo ,digestive system ,Drug Administration Schedule ,Article ,03 medical and health sciences ,Young Adult ,Genetics ,medicine ,Humans ,Acetaminophen ,Models, Genetic ,business.industry ,Gene Expression Profiling ,GeneCalling ,digestive system diseases ,Pharmacogenomic Testing ,Gene expression profiling ,stomatognathic diseases ,030104 developmental biology ,Pharmacogenetics ,RNA ,Drug Overdose ,business ,Biomarkers - Abstract
Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.
- Published
- 2015