Pharmacogenetics and Forensic Toxicology: A New Step towards a Multidisciplinary Approach

Abstract

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice.

Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the CHRNA6 Gene

“…The objective of this study was to determine whether the human CHRNA6 3′-UTR knock-in is functional using the human CHRNA6 3′-UTR rat lines. Gene-drug association studies (i.e., pharmacogenetics) are necessary to understand how genetics affect the response to drugs [ 32 , 33 , 34 ]. Given that genetic factors influence tobacco product use [ 35 ], this study assessed how a SNP in the 3′-UTR of the CHRNA 6 gene affects nicotine-induced behaviors during a critical time in development, adolescence.…”

A Forensic Diagnostic Algorithm for Drug-Related Deaths: A Case Series

“…Further efforts are needed to standardize toxicological testing for forensic purposes and improve technical developments of laboratory testing to improve laboratory capacity and meet high-quality and standardized requirements [8][9][10]29]. Postmortem concentrations must be interpreted according to all other findings of other forensic disciplines [27,33,40]. Moreover, all the conclusions collected must be related to the recent evidence provided by the literature to establish the cause and manner of death.Further efforts are needed to improve communication with other stakeholders (police, justice, health system), to undertake prevention and public health measures.…”

The Impact of Pharmacogenetics on Pharmacokinetics and Pharmacodynamics in Neonates and Infants: A Systematic Review

“… 7 Using the same approach, PG holds the promise in related fields of neonatal medicine, like forensic medicine and sudden infant death syndrome. 8 …”