0000000000260932

AUTHOR

Markus A. Schirmer

showing 2 related works from this author

Reduction of nevirapine-driven HIV mutations by carbamazepine is modulated by CYP3A activity

2014

Item does not contain fulltext OBJECTIVES: The reduction in mother-to-child transmission of HIV-1 by single-dose nevirapine given at birth onset is achieved at the expense of de novo HIV-1 resistance mutations. In the VITA1 study, single-dose carbamazepine accelerated nevirapine elimination, but the accompanying trend towards fewer de novo HIV-1 mutations was statistically non-significant. METHODS: We investigated if the effect of carbamazepine was confounded by the individual variability in nevirapine metabolism and transport. RESULTS: Nine of 34 (26%) single-dose nevirapine-treated women had one or more nevirapine-associated resistance mutations, compared with 3 of 34 (9%) in the single-d…

Microbiology (medical)NevirapineCYP3AAnti-HIV AgentsHuman immunodeficiency virus (HIV)Mutation MissenseEndogenyHIV InfectionsPharmacologyBiologymedicine.disease_causeChemopreventionPregnancyDrug Resistance ViralmedicineClinical endpointCytochrome P-450 CYP3AHumansPharmacology (medical)NevirapinePharmacologyMutationCYP3A4Cytochrome P-450 CYP3A InducersCarbamazepinelnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]Infectious DiseasesCarbamazepineTreatment OutcomeHIV-1Femalemedicine.drug
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Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations.

2005

Cytochrome P450 3A enzymes (CYP3A) play a major role in the metabolism of steroid hormones, drugs and other chemicals, including many carcinogens. The individually variable CYP3A expression, which remains mostly unexplained, has been suggested to affect clinical phenotypes. We investigated the CYP3A locus in five ethnic groups. The degree of linkage disequilibrium (LD) differed among ethnic groups, but the most common alleles of the conserved LD regions were remarkably similar. Non-African haplotypes are few; for example, only four haplotypes account for 80% of common European Caucasian alleles. Large LD blocks of high frequencies were suggestive of selection. Accordingly, European Caucasia…

Linkage disequilibriumPopulationBlack PeopleSingle-nucleotide polymorphismLocus (genetics)BiologyLinkage DisequilibriumWhite PeopleAsian PeopleCytochrome P-450 Enzyme SystemGeneticsCytochrome P-450 CYP3AHumansGeneral Pharmacology Toxicology and PharmaceuticsAlleleSelection GeneticeducationCYP3A5Molecular BiologyGenetics (clinical)AllelesGeneticseducation.field_of_studyHaplotypeGenetic VariationHaplotypesLiverMolecular MedicinePharmacogeneticsPharmacogenetics and genomics
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