ArticleEnvironmental health perspectives2009
Molecular population genetics of human CYP3A locus: signatures of positive selection and implications for evolutionary environmental medicine.
Article in Environmental health perspectives, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Pharmacodynamics, pharmacokinetics, and safety of ticagrelor in Chinese patients with stable coronary artery disease.British journal of clinical pharmacology · 2016Trial
- Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients.Acta pharmacologica Sinica · 2015Trial
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- A Comparison of Molecular Techniques for Improving the Methodology in the Laboratory of Pharmacogenetics.International journal of molecular sciences · 2024Article
- Signatures of Co-evolution and Co-regulation in the CYP3A and CYP4F Genes in Humans.Genome biology and evolution · 2024Article
- Cocaine-Induced Time-Dependent Alterations in Cytochrome P450 and Liver Function.International journal of molecular sciences · 2023Review
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Genetic ancestry plays a central role in population pharmacogenomics.Communications biology · 2021Article
- Is there adaptation in the human genome for taste perception and phase I biotransformation?BMC evolutionary biology · 2019Article
- PharmGKB summary: clozapine pathway, pharmacokinetics.Pharmacogenetics and genomics · 2018Article
- A 6-week laboratory research rotation in pharmacogenomics: a model for preparing pharmacy students to practice precision medicine.The pharmacogenomics journal · 2018Article
- Ancestry-Adjusted Vitamin D Metabolite Concentrations in Association With Cytochrome P450 3A Polymorphisms.American journal of epidemiology · 2018Article
- Article
- Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery.Current drug metabolism · 2017Review
- Molecular diversity and population structure at the Cytochrome P450 3A5 gene in Africa.BMC genetics · 2013Article
- Human loci involved in drug biotransformation: worldwide genetic variation, population structure, and pharmacogenetic implications.Human genetics · 2013Article
- Pharmacogenomics of Cytochrome P450 3A4: Recent Progress Toward the "Missing Heritability" Problem.Frontiers in genetics · 2013Article
- African variation at Cytochrome P450 genes: Evolutionary aspects and the implications for the treatment of infectious diseases.Evolution, medicine, and public health · 2013Article
- Pharmacokinetics and tolerability of single and multiple doses of ticagrelor in healthy Chinese subjects: an open-label, sequential, two-cohort, single-centre study.Clinical drug investigation · 2012Article
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe human CYP3A gene cluster codes for cytochrome P450 (CYP) subfamily enzymes that catalyze the metabolism of various exogenous and endogenous chemicals and is an obvious candidate for evolutionary and environmental genomic study. Functional variants in the CYP3A locus may have undergone a selective sweep in response to various environmental conditions.
objectiveThe goal of this study was to profile the allelic structure across the human CYP3A locus and investigate natural selection on that locus.
methodsFrom the CYP3A locus spanning 231 kb, we resequenced 54 genomic DNA fragments (a total of 43,675 bases) spanning four genes (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) and two pseudogenes (CYP3AP1 and CYP3AP2), and randomly selected intergenic regions at the CYP3A locus in Africans (24 individuals), Caucasians (24 individuals), and Chinese (29 individuals). We comprehensively investigated the nucleotide diversity and haplotype structure and examined the possible role of natural selection in shaping the sequence variation throughout the gene cluster.
resultsNeutrality tests with Tajima's D, Fu and Li's D* and F*, and Fay and Wu's H indicated possible roles of positive selection on the entire CYP3A locus in non-Africans. Sliding-window analyses of nucleotide diversity and frequency spectrum, as well as haplotype diversity and phylogenetically inferred haplotype structure, revealed that CYP3A4 and CYP3A7 had recently undergone or were undergoing a selective sweep in all three populations, whereas CYP3A43 and CYP3A5 were undergoing a selective sweep in non-Africans and Caucasians, respectively.
conclusionThe refined allelic architecture and selection spectrum for the human CYP3A locus highlight that evolutionary dynamics of molecular adaptation may underlie the phenotypic variation of the xenobiotic disposition system and varied predisposition to complex disorders in which xenobiotics play a role.
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