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, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37503696
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Infections
/
Anti-HIV Agents
/
Pre-Exposure Prophylaxis
Limits:
Female
/
Humans
Country/Region as subject:
Africa
Language:
En
Journal:
Pharmacogenomics
Journal subject:
FARMACOLOGIA
/
GENETICA MEDICA
Year:
2023
Document type:
Article
Affiliation country: