J. Steven Leeder

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Polymorphic expression of CYP2D6 contributes to the wide range of activity observed for this clinically important drug metabolizing enzyme. In this report we describe novel CYP2D7/2D6 hybrid genes encoding non-functional and functional CYP2D6 protein and a CYP2D7 variant that mimics a CYP2D7/2D6 hybrid gene. Five-kilobyte-long PCR products encompassing the(More)
Rapid developments in molecular technology have yielded a large amount of high throughput genetic data to understand the mechanism for complex traits. The increase of genetic variants requires hundreds and thousands of statistical tests to be performed simultaneously in analysis, which poses a challenge to control the overall Type I error rate. Combining(More)
CYP2D6 contributes to the metabolism of many clinically used drugs and is increasingly tested to individualize drug therapy. The CYP2D6 gene is challenging to genotype due to the highly complex nature of its gene locus. TaqMan technology is widely used in the clinical and research settings for genotype analysis due to assay reliability, low cost, and the(More)
Although methotrexate is widely used in clinical practice there remains significant lack of understanding of its mechanisms of action and the factors that contribute to the variability in toxicity and response seen clinically. In addition to differences in drug administration, factors that affect pharmacokinetics and pharmacodynamics such as genetic(More)
  • Susan M. Abdel-Rahman, Matthew L. Breitkreutz, Charlie Bi, Brett J. Matzuka, Jignesh Dalal, K. Leigh Casey +5 others
  • 2016
BACKGROUND Busulfan demonstrates a narrow therapeutic index for which clinicians routinely employ therapeutic drug monitoring (TDM). However, operationalizing TDM can be fraught with inefficiency. We developed and tested software encoding a clinical decision support tool (DST) that is embedded into our electronic health record (EHR) and designed to(More)
Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age- and sex-matched(More)
TaqMan™ genotyping assays are widely used to genotype CYP2D6, which encodes a major drug metabolizing enzyme. Assay design for CYP2D6 can be challenging owing to the presence of two pseudogenes, CYP2D7 and CYP2D8, structural and copy number variation and numerous single nucleotide polymorphisms (SNPs) some of which reflect the wild-type sequence of the(More)
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