Genetic Diversity of Variants Involved in Drug Response Among Tunisian and Italian Populations Toward Personalized Medicine

Overview

Journal Sci Rep

Specialty Science

Date 2024 Mar 11

PMID 38462643

Authors

Haifa Jmel

Stefania Sarno

Cristina Giuliani

Wided Boukhalfa

Sonia Abdelhak

Donata Luiselli

Rym Kefi

Affiliations

Soon will be listed here.

Abstract

Adverse drug reactions (ADR) represent a significant contributor to morbidity and mortality, imposing a substantial financial burden. Genetic ancestry plays a crucial role in drug response. The aim of this study is to characterize the genetic variability of selected pharmacogenes involved with ADR in Tunisians and Italians, with a comparative analysis against global populations. A cohort of 135 healthy Tunisians and 737 Italians were genotyped using a SNP array. Variants located in 25 Very Important Pharmacogenes implicated in ADR were extracted from the genotyping data. Distribution analysis of common variants in Tunisian and Italian populations in comparison to 24 publicly available worldwide populations was performed using PLINK and R software. Results from Principle Component and ADMIXTURE analyses showed a high genetic similarity among Mediterranean populations, distinguishing them from Sub-Saharan African and Asian populations. The Fst comparative analysis identified 27 variants exhibiting significant differentiation between the studied populations. Among these variants, four SNPs rs622342, rs3846662, rs7294, rs5215 located in SLC22A1, HMGCR, VKORC1 and KCNJ11 genes respectively, are reported to be associated with ethnic variability in drug responses. In conclusion, correlating the frequencies of genotype risk variants with their associated ADRs would enhance drug outcomes and the implementation of personalized medicine in the studied populations.

Citing Articles

Statin Use in Children and Adolescents - Dos, Don'ts and Practical Tips.

Wilson D, Patel M Curr Atheroscler Rep. 2024; 27(1):16.

PMID: 39636514 DOI: 10.1007/s11883-024-01256-w.

CYP2C gene polymorphisms in North African populations.

Messaoudi M, Pakstis A, Boussetta S, Ben Ammar Elgaaied A, Kidd K, Cherni L Mol Biol Rep. 2024; 51(1):1145.

PMID: 39532754 DOI: 10.1007/s11033-024-10093-8.

Pharmacogenetics in Italy: current landscape and future prospects.

Floris M, Moschella A, Alcalay M, Montella A, Tirelli M, Fontana L Hum Genomics. 2024; 18(1):78.

PMID: 38987819 PMC: 11234611. DOI: 10.1186/s40246-024-00612-w.

References

Chan S, Jin S, Loh M, Brunham L . Progress in understanding the genomic basis for adverse drug reactions: a comprehensive review and focus on the role of ethnicity. Pharmacogenomics. 2015; 16(10):1161-78. DOI: 10.2217/pgs.15.54. View

Sultana J, Cutroneo P, Trifiro G . Clinical and economic burden of adverse drug reactions. J Pharmacol Pharmacother. 2013; 4(Suppl 1):S73-7. PMC: 3853675. DOI: 10.4103/0976-500X.120957. View

Lakiotaki K, Kanterakis A, Kartsaki E, Katsila T, Patrinos G, Potamias G . Exploring public genomics data for population pharmacogenomics. PLoS One. 2017; 12(8):e0182138. PMC: 5542428. DOI: 10.1371/journal.pone.0182138. View

Giri A, Khan N, Basu A, Tandon N, Scaria V, Bharadwaj D . Pharmacogenetic landscape of clopidogrel in north Indians suggest distinct interpopulation differences in allele frequencies. Pharmacogenomics. 2014; 15(5):643-53. DOI: 10.2217/pgs.13.241. View

Umamaheswaran G, Kumar D, Adithan C . Distribution of genetic polymorphisms of genes encoding drug metabolizing enzymes & drug transporters - a review with Indian perspective. Indian J Med Res. 2014; 139(1):27-65. PMC: 3994740. View

Wood A, Zhou H . Ethnic differences in drug disposition and responsiveness. Clin Pharmacokinet. 1991; 20(5):350-73. DOI: 10.2165/00003088-199120050-00002. View

Wang L, Aikemu A, Yibulayin A, Du S, Geng T, Wang B . Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China. BMC Genet. 2015; 16:66. PMC: 4475291. DOI: 10.1186/s12863-015-0232-x. View

Weinshilboum R . Inheritance and drug response. N Engl J Med. 2003; 348(6):529-37. DOI: 10.1056/NEJMra020021. View

Bank P, Swen J, Guchelaar H . Implementation of Pharmacogenomics in Everyday Clinical Settings. Adv Pharmacol. 2018; 83:219-246. DOI: 10.1016/bs.apha.2018.04.003. View

10.

Zhou Z, Chen X, Sneed K, Yang Y, Zhang X, He Z . Clinical association between pharmacogenomics and adverse drug reactions. Drugs. 2015; 75(6):589-631. DOI: 10.1007/s40265-015-0375-0. View

11.

Cacabelos R, Cacabelos N, Carril J . The role of pharmacogenomics in adverse drug reactions. Expert Rev Clin Pharmacol. 2019; 12(5):407-442. DOI: 10.1080/17512433.2019.1597706. View

12.

Lauschke V, Ingelman-Sundberg M . Prediction of drug response and adverse drug reactions: From twin studies to Next Generation Sequencing. Eur J Pharm Sci. 2019; 130:65-77. DOI: 10.1016/j.ejps.2019.01.024. View

13.

Taylor C, Crosby I, Yip V, Maguire P, Pirmohamed M, Turner R . A Review of the Important Role of in Pharmacogenomics. Genes (Basel). 2020; 11(11). PMC: 7692531. DOI: 10.3390/genes11111295. View

14.

Ingelman-Sundberg M . Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med. 2001; 250(3):186-200. DOI: 10.1046/j.1365-2796.2001.00879.x. View

15.

Ramamoorthy A, Pacanowski M, Bull J, Zhang L . Racial/ethnic differences in drug disposition and response: review of recently approved drugs. Clin Pharmacol Ther. 2015; 97(3):263-73. DOI: 10.1002/cpt.61. View

16.

Bonifaz-Pena V, Contreras A, Struchiner C, Roela R, Furuya-Mazzotti T, Chammas R . Exploring the distribution of genetic markers of pharmacogenomics relevance in Brazilian and Mexican populations. PLoS One. 2014; 9(11):e112640. PMC: 4242606. DOI: 10.1371/journal.pone.0112640. View

17.

Ingelman-Sundberg M, Sim S, Gomez A, Rodriguez-Antona C . Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007; 116(3):496-526. DOI: 10.1016/j.pharmthera.2007.09.004. View

18.

Frigi S, Mota-Vieira L, Cherni L, van Oven M, Pires R, Boussetta S . Mitochondrial DNA analysis of Tunisians reveals a mosaic genetic structure with recent population expansion. Homo. 2017; 68(4):298-315. DOI: 10.1016/j.jchb.2017.05.003. View

19.

Fadhlaoui-Zid K, Martinez-Cruz B, Khodjet-El-Khil H, Mendizabal I, Benammar-Elgaaied A, Comas D . Genetic structure of Tunisian ethnic groups revealed by paternal lineages. Am J Phys Anthropol. 2011; 146(2):271-80. DOI: 10.1002/ajpa.21581. View

20.

Jmel H, Romdhane L, Ben Halima Y, Hechmi M, Naouali C, Dallali H . Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations. PLoS One. 2018; 13(4):e0194842. PMC: 5898725. DOI: 10.1371/journal.pone.0194842. View