Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Pharmacogenomics - 24(2023), 11 vom: 01. Juli, Seite 599-613 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zondo, Nomusa M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.09.2023 Date Revised 11.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.2217/pgs-2023-0058 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360036066 |
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| 245 | 1 | 0 | |a 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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| 500 | |a Date Revised 11.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a ATP-binding cassette drug transporters | |
| 650 | 4 | |a African women | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a South Africa | |
| 650 | 4 | |a Truvada® | |
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| 700 | 1 | |a Mansoor, Leila E |e verfasserin |4 aut | |
| 700 | 1 | |a Mahomed, Sharana |e verfasserin |4 aut | |
| 700 | 1 | |a Lewis, Lara |e verfasserin |4 aut | |
| 700 | 1 | |a Ramsuran, Veron |e verfasserin |4 aut | |
| 700 | 1 | |a Archary, Derseree |e verfasserin |4 aut | |
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