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 |
|
uct.type.filetype |
Image |
|
dc.identifier.apacitation |
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. <i>Human Genomics</i>, http://hdl.handle.net/11427/14522 |
en_ZA |
dc.identifier.chicagocitation |
Matimba, Alice, Jurgen Del-Favero, Christine Van Broeckhoven, and Collen Masimirembwa "Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects." <i>Human Genomics</i> (2009) http://hdl.handle.net/11427/14522 |
en_ZA |
dc.identifier.vancouvercitation |
Matimba A, Del-Favero J, Van Broeckhoven C, Masimirembwa C. Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects. Human Genomics. 2009; http://hdl.handle.net/11427/14522. |
en_ZA |
dc.identifier.ris |
TY - Journal Article
AU - Matimba, Alice
AU - Del-Favero, Jurgen
AU - Van Broeckhoven, Christine
AU - Masimirembwa, Collen
AB - 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.
DA - 2009
DB - OpenUCT
DO - 10.1186/1479-7364-3-2-169
DP - University of Cape Town
J1 - Human Genomics
LK - https://open.uct.ac.za
PB - University of Cape Town
PY - 2009
T1 - Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects
TI - Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects
UR - http://hdl.handle.net/11427/14522
ER -
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en_ZA |