Pharmacogenetics of Artemether-Lumefantrine Combination Therapyadmin
The pharmacogenetics of Artemether-Lumefantrine Combination Therapy for Uncomplicated Plasmodium falciparum Malaria in Sudan
Hamad Alneel Albagir Ahmed Ali 1, Muntaser Ibrahim 2*
1Department of Microbiology, International University of Africa
2Institute of Endemic Diseases, University Of Khartoum
Background: Artemether-lumefantrine combination currently recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria in Sudan and substrates of Cytochrome P450 enzymes.
Significant inter-individual variability in the disposition of these drugs has been documented, suggesting the possibility of the influence of genetic factors. It is; therefore, important to obtain the pharmacogenetic profile (or spectrum) of the population in Sudan with respect to these combinations and thereby enable practitioners to predict treatment outcome. The aim of this study was to determine the presence of Cytochrome P450 variant alleles (CYP2C8*2, CYP2C8*3, CYP2B6*6, CYP3A4*1B, CYP3A5*3, and CYP3A5*6 ) in Sudan where malaria is endemic.
Methods: Whole exome sequence data for 55 healthy Sudanese individuals were analyzed to determine
the allele frequencies of the variants known to impact artemether-lumefantrine combination.
Results: Allele frequencies of the variants: CYP2C8*2 (rs11572103), CYP2C8*3(rs10509681-
rs11572080), CYP2B6*6 (rs3745274), CYP3A4*1B (rs2740574), CYP3A5*3 (rs776746), CYP3A5*6
(rs10264272) were found to be 0.081, 0.045, 0.081, 0.354, 0.009, 0.200 and 0.136 respectively.
Conclusion: Prevalence of CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A5*6 and CYP2B6*6 variants are common while CYP3A4*1B variants are rare in the Sudanese Exome Data. The frequencies documented in this study are comparable to data acquired from earlier studies on African populations. Pharmacogenomics data, such as that exhibited in this paper, produce a basis for further studies on the impact of polymorphism in Artemether-lumefantrine combination safety and efficacy.
Keywords: Cytochrome P450, Artemisinin-lumefantrine combination therapy, Sudan, uncomplicated
Plasmodium falciparum malaria.