Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis

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creativework.keywords - en
African women
ATP-binding cassette drug transporters
HIV
pre-exposure prophylaxis
single-nucleotide polymorphisms
South Africa
tenofovir
Truvada®
dc.contributor.author
Zondo, Nomusa M.
Sobia, Parveen
Sivro, Aida
Ngcapu, Sinaye
Mansoor, Leila E.
Mahomed, Sharana
Lewis, Lara
Ramsuran, Veron
Archary, Derseree
dc.date.accessioned
2023-10-18T15:08:47Z
dc.date.available
2023-10-18T15:08:47Z
dc.date.issued
2023-07-28
dc.description.abstract - en
AIM: We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada® for HIV prevention. MATERIALS & METHODS: In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. RESULTS: Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the ABCC4(3463C/T) SNP had significantly higher tenofovir levels. In contrast, the AA genotype for the ABCC4(4976A/G) SNP showed significantly less tenofovir, while mRNA expression was increased. CONCLUSION: SNPs in the ABCC4 gene may differentially affect gene expression and circulating tenofovir. Their impact may inform on low pre-exposure prophylaxis efficacy and discern effective drugs in clinical trials of African women enriched for certain genotypes.
dc.identifier.citation
Zondo, N. M., Sobia, P., Sivro, A., Ngcapu, S., Mansoor, L. E., Mahomed, S., Lewis, L., Ramsuran, V., & Archary, D. (2023). Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis. Pharmacogenomics, 24(11), 599–613. https://doi.org/10.2217/pgs-2023-0058
dc.identifier.doi
https://doi.org/10.2217/pgs-2023-0058
dc.identifier.issn
1744-8042
dc.identifier.pubmedID
37503696
dc.identifier.uri
https://open-science.canada.ca/handle/123456789/1223
dc.language.iso
en
dc.publisher
Future Medicine, an imprint of Future Science Group
dc.rights - en
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.rights - fr
Creative Commons Attribution - Pas d'utilisation commerciale - Pas de modification 4.0 International (CC BY-NC-ND 4.0)
dc.rights.uri - en
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.uri - fr
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
dc.subject - en
Health
dc.subject - fr
Santé
dc.subject.en - en
Health
dc.subject.fr - fr
Santé
dc.title - en
Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis
dc.type - en
Article
dc.type - fr
Article
local.article.journalissue
11
local.article.journaltitle
Pharmacogenomics
local.article.journalvolume
24
local.pagination
599–613
local.peerreview - en
Yes
local.peerreview - fr
Oui
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