Human host and malaria parasite genome variations to susceptibility to malaria
type: CreativeWork
description: Background: Inter-ethnic differences in response to medication can be explained through population structure as observed from genetic variants affecting drug metabolism. Antimalarial drugs are used in populations carrying different profiles of genetic variability. However, there is limited information on the distribution of genetic variants of pharmacogenomics importance in African populations. Aims: We set out to determine whether there are differences in the pharmacogenetic profiles when comparing populations residing in malaria endemic and non-endemic areas. Methodology: Genome-wide genotype datasets (n=13, 447) from four malaria endemic African populations, including Mali, Kenya, Gambia, and Malawi, which were part of the MalariaGEN consortium, were accessed. As comparator, reference datasets of global populations comprising of 20 ethnic groups (n~5,000) from African Genome Variation Project (AGVP) and 1000 Genome consortium project were accessed, considering their malaria epidemiology. Pharmacogenes that are verified from databases such as PharmVar and PharmGKB, and nomenclature sites for uridine 5'-diphospho-glucuronosyltransferases (UGT), solute carrier (SLC) transporters, ATP-binding cassette (ABC) transporters, thiopurine Smethyl transferase (TPMT), and N-acetyltransferases (NAT) were used. Pharmacogenes reported to affect antimalarial drugs were noted and their distribution analysed. Single nucleotide polymorphisms (SNPs) that map to pharmacogenes were retrieved from dbSNP databases and used in the comparison of the populations from malaria endemic and nonendemic regions, through population structure evaluation using pharmacogenes variants. As part of confirmation, genotyping for CYP2C8 SNPs was carried out in native South African population groups, which we have access to our laboratory. CYP2C8 is particularly interesting because of its central involvement in the metabolism of some of the major antimalarial drugs. Results: There were quantitative and qual…
abstract: Background: Inter-ethnic differences in response to medication can be explained through population structure as observed from genetic variants affecting drug metabolism. Antimalarial drugs are used in populations carrying different profiles of genetic variability. However, there is limited information on the distribution of genetic variants of pharmacogenomics importance in African populations. Aims: We set out to determine whether there are differences in the pharmacogenetic profiles when comparing populations residing in malaria endemic and non-endemic areas. Methodology: Genome-wide genotype datasets (n=13, 447) from four malaria endemic African populations, including Mali, Kenya, Gambia, and Malawi, which were part of the MalariaGEN consortium, were accessed. As comparator, reference datasets of global populations comprising of 20 ethnic groups (n~5,000) from African Genome Variation Project (AGVP) and 1000 Genome consortium project were accessed, considering their malaria epidemiology. Pharmacogenes that are verified from databases such as PharmVar and PharmGKB, and nomenclature sites for uridine 5'-diphospho-glucuronosyltransferases (UGT), solute carrier (SLC) transporters, ATP-binding cassette (ABC) transporters, thiopurine Smethyl transferase (TPMT), and N-acetyltransferases (NAT) were used. Pharmacogenes reported to affect antimalarial drugs were noted and their distribution analysed. Single nucleotide polymorphisms (SNPs) that map to pharmacogenes were retrieved from dbSNP databases and used in the comparison of the populations from malaria endemic and nonendemic regions, through population structure evaluation using pharmacogenes variants. As part of confirmation, genotyping for CYP2C8 SNPs was carried out in native South African population groups, which we have access to our laboratory. CYP2C8 is particularly interesting because of its central involvement in the metabolism of some of the major antimalarial drugs. Results: There were quantitative and qual…
author: Hordofa, Hundaol
keywords: Medicine
date published: 2023
date modified: 2026-07-24T01:33:36Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Clinical Laboratory Sciences

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property ID: Handle
value: http://hdl.handle.net/11427/39472