Metabolic ratios and SNPs implicated in tramadol-related deaths

Aly, Sanaa M.; Hakim, Florian; Richeval, Camille; Hennart, Benjamin; Gaulier, Jean-Michel; Allorge, Delphine

Document type :

Article dans une revue scientifique: Article original

DOI :

10.1007/s00414-023-03052-8

PMID :

37460702

Permalink :

http://hdl.handle.net/20.500.12210/88388

Title :

Metabolic ratios and SNPs implicated in tramadol-related deaths

Author(s) :

Aly, Sanaa M. [Auteur]
Suez Canal University
Toxicologie et Génopathies [CHRU Lille]
Hakim, Florian [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Toxicologie et Génopathies [CHRU Lille]
Richeval, Camille [Auteur]

Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Toxicologie et Génopathies [CHRU Lille]
Hennart, Benjamin [Auteur]

Toxicologie et Génopathies [CHRU Lille]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Gaulier, Jean-Michel [Auteur]

Toxicologie et Génopathies [CHRU Lille]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Allorge, Delphine [Auteur]

Toxicologie et Génopathies [CHRU Lille]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Journal title :

International Journal of Legal Medicine

Abbreviated title :

Int J Legal Med

Volume number :

137

Pages :

1431–1437

Publisher :

Springer

Publication date :

2023-07-17

ISSN :

0937-9827

English keyword(s) :

Next-generation sequencing
Forensic toxicology
Postmortem
CYP2D6
CYP2B6
CYP3A4

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille
Institut Pasteur de Lille

Collections :

IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Submission date :

2023-10-20T05:46:52Z
2024-02-21T13:14:52Z

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Version	Link	Modification date
2	20.500.12210/88388*	2024-02-21T13:01:58Z
1	20.500.12210/88388.1	2023-10-20T05:46:52Z

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