Metabolic ratios and SNPs implicated in tramadol-related deaths.
CYP2B6
CYP2D6
CYP3A4
Forensic toxicology
Next-generation sequencing
Postmortem
Journal
International journal of legal medicine
ISSN: 1437-1596
Titre abrégé: Int J Legal Med
Pays: Germany
ID NLM: 9101456
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
15
03
2023
accepted:
20
06
2023
pubmed:
18
7
2023
medline:
18
7
2023
entrez:
17
7
2023
Statut:
ppublish
Résumé
Tramadol (TR) metabolism is performed by polymorphic enzymes that are influenced by genetic polymorphisms. Within this scope, the study presented here aimed to describe 41 genetic variants within CYP2D6, CYP2B6, and CYP3A4 genes in 48 cases of TR-related death that may be involved in the response to TR and to assess whether there is a correlation between these genetic variants and metabolic ratios (MRs). Blood samples from 48 victims of a TR-related death were analyzed to determine the concentrations of TR and its metabolites [O-desmethyltramadol (M1) & N-desmethyltramadol (M2)] using a LC-MS/MS method. All the samples were also genotyped for 41 common CYP2D6, CYP2B6, and CYP3A4 single nucleotide polymorphisms (SNPs) using the HaloPlex Target Enrichment system. Cases with the T/- genotype (rs35742686 in CYP2D6) had significantly higher M2/M1 ratio than cases with T/T genotype and cases with the G/A genotype (rs35599367 in CYP3A4) had significantly higher MR2 (TR/M2) ratio than cases with G/G genotype. The frequency of tested SNPs which belong to CYP2D6, CYP2B6, and CYP3A4 revealed the over-presentation of 2 SNPs (rs1058172 in CYP2D6 and rs4803419 in CYP2B6) in TR overdose group, which could have toxicological implications. These results indicate these polymorphisms in CYP2D6, CYP2B6, and CYP3A4 might influence the function and could increase the risk of toxicity. However, these findings should be supported in future studies with larger groups of cases.
Identifiants
pubmed: 37460702
doi: 10.1007/s00414-023-03052-8
pii: 10.1007/s00414-023-03052-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1431-1437Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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