ArticleThe pharmacogenomics journal2009
Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.
Article in The pharmacogenomics journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin.European journal of clinical pharmacology · 2013Trial
- CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease.American journal of nephrology · 2010Trial
- Development and validation of a method for the simultaneous quantification of endogenous steroids metabolized by CYP3A.Translational and clinical pharmacology · 2020Article
- Distribution of Exogenous and Endogenous CYP3A Markers and Related Factors in Healthy Males and Females.The AAPS journal · 2017Article
- Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Pharmacogenomics of Cytochrome P450 3A4: Recent Progress Toward the "Missing Heritability" Problem.Frontiers in genetics · 2013Article
- The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy.Journal of personalized medicine · 2012Article
- Role of pharmacogenomics in the management of traditional and novel oral anticoagulants.Pharmacotherapy · 2011Review
- Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs.The pharmacogenomics journal · 2011Article
- The missing association: sequencing-based discovery of novel SNPs in VKORC1 and CYP2C9 that affect warfarin dose in African Americans.Clinical pharmacology and therapeutics · 2011Article
- Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium.Transplantation · 2011Article
- Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment.Annals of the New York Academy of Sciences · 2010Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The CYP3A locus encodes hepatic enzymes that metabolize many clinically used drugs. However, there is marked interindividual variability in enzyme expression and clearance of drugs metabolized by these enzymes. We utilized comparative genomics and computational prediction of transcriptional factor binding sites to evaluate regions within CYP3A that were most likely to contribute to this variation. We then used a haplotype tagging single-nucleotide polymorphisms (htSNPs) approach to evaluate the entire locus with the fewest number of maximally informative SNPs. We investigated the association between these htSNPs and in vivo CYP3A enzyme activity using a single-point IV midazolam clearance assay. We found associations between the midazolam phenotype and age, diagnosis of hypertension and one htSNP (141689) located upstream of CYP3A4. 141689 lies near the xenobiotic responsive enhancer module (XREM) regulatory region of CYP3A4. Cell-based studies show increased transcriptional activation with the minor allele at 141689, in agreement with the in vivo association study findings. This study marks the first systematic evaluation of coding and noncoding variation that may contribute to CYP3A phenotypic variability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.