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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 26, Number 7, October 2002,
pp. 438-447
Pharmacogenomics as Molecular Autopsy for Postmortem Forensic
Toxicology: Genotyping Cytochrome P450 2D6 for Oxycodone Cases
Paul J. Jannetto[1],[2], Steven H. Wong[1],[2],
Susan B. Gock[1],[2], Elvan Laleli-Sahin[1],[2], B. Charles Schur[2], and Jeffrey
M. Jentzen[1],[2]
[1]Milwaukee County Medical Examiner’s Office, Milwaukee, Wisconsin
[2]Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
Pharmacogenomics, the study
of the impact of heritable traits on pharmacology and toxicology, may serve
as an adjunct for certifying opioid fatalities. Oxycodone, frequently prescribed
for the relief of moderate to severe pain, is metabolized by cytochrome P450
(CYP) 2D6, encoded by a polymorphic gene with three mutations (*3, *4, and *5)
with a combined 95% allelic frequency and about 10% prevalence. Individuals
with variant alleles are more susceptible to oxycodone toxicity. By assessing
the prevalence of CYP2D6 polymorphisms and covariables, we hypothesized that
oxycodone fatality may be partially due to poor drug metabolism caused by CYP2D6
variant alleles. From the Milwaukee County Medical Examiner’s Office (MCMEO),
a retrospective analysis of 15 oxycodone cases was followed by genotyping blood
samples for the variant alleles by conventional and real-time PCRs. Institutional
Review Board approval was obtained. Oxycodone, extracted from blood and/or urine,
was quantitated by GC–MS. The results show two homozygous for 2D6*4 and
four heterozygous for 2D6*4. The MCMEO was not significantly different from
those in the control group (n = 26) (p > 0.05, Fisher’s Exact Test).
However, genotyping CYP2D6 provided a more definitive interpretation of the
oxycodone toxicity in four cases. Therefore, pharmacogenomics may serve as an
adjunct in the determination of the cause and manner of death in forensic toxicology
and a pharmacogenomic algorithm for genotyping has been proposed. Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
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