Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis
- DOI
- Language of the publication
- English
- Date
- 2023-07-28
- Type
- Article
- Author(s)
- Zondo, Nomusa M.
- Sobia, Parveen
- Sivro, Aida
- Ngcapu, Sinaye
- Mansoor, Leila E.
- Mahomed, Sharana
- Lewis, Lara
- Ramsuran, Veron
- Archary, Derseree
- Publisher
- Future Medicine, an imprint of Future Science Group
Abstract
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.
Subject
- Health
Keywords
- African women,
- ATP-binding cassette drug transporters,
- HIV,
- pre-exposure prophylaxis,
- single-nucleotide polymorphisms,
- South Africa,
- tenofovir,
- Truvada®
Rights
Pagination
599–613
Peer review
Yes
Identifiers
- PubMed ID
- 37503696
- ISSN
- 1744-8042
Article
- Journal title
- Pharmacogenomics
- Journal volume
- 24
- Journal issue
- 11
Citation(s)
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