A genome-wide association study of tramadol metabolism from post-mortem samples

Frank R. Wendt, Anna Liina Rahikainen, Jonathan L. King, Antti Sajantila, Bruce Budowle

Research output: Contribution to journalArticle

Abstract

Phase I tramadol metabolism requires cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) to form O-desmethyltramadol (M1). CYP2D6 genetic variants may infer metabolizer phenotype; however, drug ADME (absorption, distribution, metabolism, and excretion) and response depend on protein pathway(s), not CYP2D6 alone. There is a paucity of data regarding the contribution of trans-acting proteins to idiosyncratic phenotypes following drug exposure. A genome-wide association study identified five markers (rs79983226/kgp11274252, rs9384825, rs62435418/kgp10370907, rs72732317/kgp3743668, and rs184199168/exm1592932) associated with the conversion of tramadol to M1 (M1:T). These SNPs reside within five genes previously implicated with adverse reactions. Analysis of accompanying toxicological meta-data revealed a significant positive linear relationship between M1:T and degree of sample polypharmacy. Taken together, these data identify candidate loci for potential clinical inferences of phenotype following exposure to tramadol and highlight sample polypharmacy as a possible diagnostic covariate in post-mortem genetic studies.

Original languageEnglish
JournalPharmacogenomics Journal
DOIs
StatePublished - 1 Jan 2019

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Tramadol
Genome-Wide Association Study
Polypharmacy
Phenotype
Peptides
Pharmaceutical Preparations
Toxicology
Single Nucleotide Polymorphism
Proteins
Genes
Cytochrome P450 Family 2

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Wendt, Frank R. ; Rahikainen, Anna Liina ; King, Jonathan L. ; Sajantila, Antti ; Budowle, Bruce. / A genome-wide association study of tramadol metabolism from post-mortem samples. In: Pharmacogenomics Journal. 2019.
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A genome-wide association study of tramadol metabolism from post-mortem samples. / Wendt, Frank R.; Rahikainen, Anna Liina; King, Jonathan L.; Sajantila, Antti; Budowle, Bruce.

In: Pharmacogenomics Journal, 01.01.2019.

Research output: Contribution to journalArticle

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