Pharmacogenetic landscape of pain management variants among Mediterranean populations.

Autor:	Jmel H; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia.; Genetic Typing Service, Institut Pasteur de Tunis, Tunis, Tunisia.; University of Tunis El Manar, Tunis, Tunisia., Boukhalfa W; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia.; Genetic Typing Service, Institut Pasteur de Tunis, Tunis, Tunisia.; University of Tunis El Manar, Tunis, Tunisia.; Faculty of Medicine of Tunis, Tunis, Tunisia., Gouiza I; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia.; Genetic Typing Service, Institut Pasteur de Tunis, Tunis, Tunisia.; University of Tunis El Manar, Tunis, Tunisia.; Faculty of Medicine of Tunis, Tunis, Tunisia.; MitoLab Team, Unité MitoVasc, Unité Mixte de Recherche Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1083, SFR ICAT, University of Angers, Angers, France., Seghaier RO; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia., Dallali H; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia.; Genetic Typing Service, Institut Pasteur de Tunis, Tunis, Tunisia.; University of Tunis El Manar, Tunis, Tunisia., Kefi R; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia.; Genetic Typing Service, Institut Pasteur de Tunis, Tunis, Tunisia.; University of Tunis El Manar, Tunis, Tunisia.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 May 15; Vol. 15, pp. 1380613. Date of Electronic Publication: 2024 May 15 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1380613
Abstrakt:	Background: Chronic pain is a major socioeconomic burden in the Mediterranean region. However, we noticed an under-representation of these populations in the pharmacogenetics of pain management studies. In this context, we aimed 1) to decipher the pharmacogenetic variant landscape among Mediterranean populations compared to worldwide populations in order to identify therapeutic biomarkers for personalized pain management and 2) to better understand the biological process of pain management through in silico investigation of pharmacogenes pathways. Materials and Methods: We collected genes and variants implicated in pain response using the Prisma guidelines from literature and PharmGK database. Next, we extracted these genes from genotyping data of 829 individuals. Then, we determined the variant distribution among the studied populations using multivariate (MDS) and admixture analysis with R and STRUCTURE software. We conducted a Chi2 test to compare the interethnic frequencies of the identified variants. We used SNPinfo web server, miRdSNP database to identify miRNA-binding sites. In addition, we investigated the functions of the identified genes and variants using pathway enrichment analysis and annotation tools. Finally, we performed docking analysis to assess the impact of variations on drug interactions. Results: We identified 63 variants implicated in pain management. MDS analysis revealed that Mediterranean populations are genetically similar to Mexican populations and divergent from other populations. STRUCTURE analysis showed that Mediterranean populations are mainly composed of European ancestry. We highlighted differences in the minor allele frequencies of three variants (rs633, rs4680, and rs165728) located in the COMT gene. Moreover, variant annotation revealed ten variants with potential miRNA-binding sites. Finally, protein structure and docking analysis revealed that two missense variants (rs4680 and rs6267) induced a decrease in COMT protein activity and affinity for dopamine. Conclusion: Our findings revealed that Mediterranean populations diverge from other ethnic groups. Furthermore, we emphasize the importance of pain-related pathways and miRNAs to better implement these markers as predictors of analgesic responses in the Mediterranean region. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Jmel, Boukhalfa, Gouiza, Seghaier, Dallali and Kefi.)
Databáze:	MEDLINE
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