Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects

 

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dc.contributor.author Matimba, Alice en_ZA
dc.contributor.author Del-Favero, Jurgen en_ZA
dc.contributor.author Van Broeckhoven, Christine en_ZA
dc.contributor.author Masimirembwa, Collen en_ZA
dc.date.accessioned 2015-10-30T09:33:23Z
dc.date.available 2015-10-30T09:33:23Z
dc.date.issued 2009 en_ZA
dc.identifier.citation Matimba, A., Del-Favero, J., Van Broeckhoven, C., & Masimirembwa, C. (2009). Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects. Hum Genomics, 3(2), 169-190. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/14522
dc.identifier.uri http://dx.doi.org/10.1186/1479-7364-3-2-169
dc.description.abstract Pharmacogenetics enables personalised therapy based on genetic profiling and is increasingly applied in drug discovery. Medicines are developed and used together with pharmacodiagnostic tools to achieve desired drug efficacy and safety margins. Genetic polymorphism of drug-metabolising enzymes such as cytochrome P450s (CYPs) and N-acetyltransferases (NATs) has been widely studied in Caucasian and Asian populations, yet studies on African variants have been less extensive. The aim of the present study was to search for novel variants of CYP2C9, CYP2C19, CYP2D6 and NAT2 genes in Africans, with a particular focus on their prevalence in different populations, their relevance to enzyme functionality and their potential for personalised therapy. Blood samples from various ethnic groups were obtained from the AiBST Biobank of African Populations. The nine exons and exon-intron junctions of the CYP genes and exon 2 of NAT2 were analysed by direct DNA sequencing. Computational tools were used for the identification, haplotype analysis and prediction of functional effects of novel single nucleotide polymorphisms (SNPs). Novel SNPs were discovered in all four genes, grouped to existing haplotypes or assigned new allele names, if possible. The functional effects of non-synonymous SNPs were predicted and known African-specific variants were confirmed, but no significant differences were found in the frequencies of SNPs between African ethnicities. The low prevalence of our novel variants and most known functional alleles is consistent with the generally high level of diversity in gene loci of African populations. This indicates that profiles of rare variants reflecting interindividual variability might become the most relevant pharmacodiagnostic tools explaining Africans' diversity in drug response. en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source Human Genomics en_ZA
dc.source.uri http://www.humgenomics.com/ en_ZA
dc.subject.other pharmacogenetics en_ZA
dc.subject.other cytochrome P450 en_ZA
dc.subject.other N-acetyltransferase en_ZA
dc.subject.other single nucleotide polymorphisms en_ZA
dc.subject.other African populations en_ZA
dc.title Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects en_ZA
dc.type Journal Article en_ZA
dc.rights.holder 2009 Henry Stewart Publications en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Human Genetics en_ZA
uct.type.filetype Text
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This is an Open Access article distributed under the terms of the Creative Commons Attribution License Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License