TRANSCRIPTOME 2002: From Functional Genomics to Systems
Precision Gene Expression Analysis and Bioinformatics Can Track the Effect of Orally Administered, Anti-inflammatory Therapeutic Agents in Human Subjects
Victor V. Tryon, J. Emmick, N. Nicholls, J. Zuzack, D. Trollinger, J. C. Cheronis, M. P. Bevilacqua, Source Precision Medicine Inc., Boulder, CO
Differential gene expression can be used to precisely and reproducibly track the molecular responses of an individual to orally administered, anti-inflammatory therapeutic agents. Oral treatment with steroids or NSAIDS led to profound modulation in the expression of selected genes associated with the inflammatory response. A three day treatment with prednisone resulted in greater than 70% suppression of expression of IL1A and IL1B and a greater than 10 fold increase in expression of IL10. mRNA from 0.2 ml of whole, heparin anti-coagulated blood was extracted immediately post-blood draw using an aqueous method followed by cDNA synthesis. Quantitative PCR was performed with the ABI Prism 7700 instrument from Applied Biosystems. High dose ibuprofen (800 mg TID) also demonstrated an anti-inflammatory pattern, reducing the expression of selected pro-inflammatory genes including TNF. This pattern was distinguishable from that induced by treatment with steroids (e.g., ibuprofen decreased IL10 expression). Control subjects were examined over time and demonstrated a stable and reproducible pattern of gene expression using a 24 gene Precision ProfileTMfor inflammation. These observations support the clinical utility of gene expression analysis in tracking the response of an individual to anti-inflammatory therapy when such assays are conducted with controlled and reproducible levels of precision.
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