ArticleThe pharmacogenomics journal2011
Sex and CYP3A5 genotype influence total CYP3A activity: high CYP3A activity and a unique distribution of CYP3A5 variant alleles in Ethiopians.
Article in The pharmacogenomics journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients.British journal of pharmacology · 2021Trial
- Urinary 6β-Hydroxycortisol/Cortisol Ratio Most Highly Correlates With Midazolam Clearance Under Hepatic CYP3A Inhibition and Induction in Females: A Pharmacometabolomics Approach.The AAPS journal · 2016Trial
- Trial
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- Induction of hepatic CYP3A4 expression by cholesterol and cholic acid: Alterations of gene expression, microsomal activity, and pharmacokinetics.Pharmacology research & perspectives · 2024Article
- CYP2C19 and CYP2J2 genotypes predict praziquantel plasma exposure among Ethiopian school-aged children.Scientific reports · 2024Article
- Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio.International journal of molecular sciences · 2022Article
- Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.European journal of clinical pharmacology · 2022Article
- Article
- Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study.Journal of personalized medicine · 2021Article
- Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania.Frontiers in pharmacology · 2021Article
- A Physiology-Based Pharmacokinetic Framework to Support Drug Development and Dose Precision During Therapeutic Hypothermia in Neonates.Frontiers in pharmacology · 2020Review
- Population Pharmacokinetic, Pharmacogenetic, and Pharmacodynamic Analysis of Cyclophosphamide in Ethiopian Breast Cancer Patients.Frontiers in pharmacology · 2020Article
- Phenotyping of Human CYP450 Enzymes by Endobiotics: Current Knowledge and Methodological Approaches.Clinical pharmacokinetics · 2019Review
- CYP2J2Frontiers in pharmacology · 2019Article
- Long-term efavirenz pharmacokinetics is comparable between Tanzanian HIV and HIV/Tuberculosis patients with the same CYP2B6*6 genotype.Scientific reports · 2018Article
- Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations.Scientific reports · 2018Observational
- N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians.European journal of clinical pharmacology · 2018Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
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Abstract
The objectives of the this study were to assess the influence of CYP3A5 genotype and sex on the variability in total CYP3A activity and to compare 4β-hydroxycholesterol and omeprazole sulfoxidation as phenotypic markers for CYP3A activity in Ethiopians. Healthy subjects (n=150) were genotyped for CYP3A5*3, *6 and *7 using allele-specific PCR and Taqman genotyping assays. Plasma levels of 4β-hydroxycholesterol, 3 h post-dose omeprazole and omeprazole sulfone, were determined by gas chromatography-mass spectrometry and high performance liquid chromatography, respectively. The frequency of CYP3A5*1, *3, *6 and *7 was 20.5, 67.3, 12.2 and 0%, respectively. The mean plasma 4β-hydroxycholesterol level was 35.4 ng ml⁻¹. The mean 4β-hydroxycholesterol level (P=0.0001) and the 4β-hydroxycholesterol/cholesterol ratio (P=0.004) were higher in women than in men. CYP3A5 genotype significantly correlated with the plasma 4β-hydroxycholesterol concentration (P=0.003) and 4β-hydroxycholesterol/cholesterol ratio (P=0.0002). The omeprazole/omeprazole sulfone ratio was significantly correlated with 4β-hydroxycholesterol and 4β-hydroxycholesterol/cholesterol ratio in CYP3A5*0/*0 genotypes but not in individuals carrying the CYP3A5*1 allele. No correlation of omeprazole/omeprazole sulfone ratio with sex or CYP3A5 genotype was observed. A clear gene-dose effect implies plasma 4β-hydroxycholesterol level as a useful endogenous biomarker for total CYP3A activity (CYP3A5 plus CYP3A4) whereas the omeprazole/omeprazole sulfone ratio reflects mainly CYP3A4 activity. Sex and CYP3A5 genotype influence total CYP3A activity. Ethiopians display high total CYP3A activity and a unique distribution of CYP3A5 variant alleles not described hitherto.
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