ArticleClinical pharmacology and therapeutics2011
Functional characterization of liver enhancers that regulate drug-associated transporters.
Article in Clinical pharmacology and therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 16 papers.
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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.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Trial
- Identification of drug responsive enhancers by predicting chromatin accessibility change from perturbed gene expression profiles.NPJ systems biology and applications · 2024Article
- Rare Variants in theDrug metabolism and disposition: the biological fate of chemicals · 2018Article
- ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia.The pharmacogenomics journal · 2018Article
- ABCG2 regulatory single-nucleotide polymorphisms alter in vivo enhancer activity and expression.Pharmacogenetics and genomics · 2017Article
- In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- SUGP1 is a novel regulator of cholesterol metabolism.Human molecular genetics · 2016Article
- Article
- Disruption of long-range gene regulation in human genetic disease: a kaleidoscope of general principles, diverse mechanisms and unique phenotypic consequences.Human genetics · 2014Review
- A novel test for selection on cis-regulatory elements reveals positive and negative selection acting on mammalian transcriptional enhancers.Molecular biology and evolution · 2013Article
- Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model.Nature genetics · 2013Article
- GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.Nature genetics · 2013Article
- Sequence signatures extracted from proximal promoters can be used to predict distal enhancers.Genome biology · 2013Article
- The hydrodynamic tail vein assay as a tool for the study of liver promoters and enhancers.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Pharmacogene regulatory elements: from discovery to applications.Genome medicine · 2012Article
- Massively parallel functional dissection of mammalian enhancers in vivo.Nature biotechnology · 2012Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Little is known about how genetic variations in enhancers influence drug response. In this study, we investigated whether nucleotide variations in enhancers that regulate drug transporters can alter their expression levels. Using comparative genomics and liver-specific transcription factor binding site (TFBS) analyses, we identified evolutionary conserved regions (ECRs) surrounding nine liver membrane transporters that interact with commonly used pharmaceuticals. The top 50 ECRs were screened for enhancer activity in vivo, of which five--located around ABCB11, SLC10A1, SLCO1B1, SLCO1A2, and SLC47A1--exhibited significant enhancer activity. Common variants identified in a large ethnically diverse cohort (n = 272) were assayed for differential enhancer activity, and three variants were found to have significant effects on reporter activity as compared with the reference allele. In addition, one variant was associated with reduced SLCO1A2 mRNA expression levels in human liver tissues, and another was associated with increased methotrexate (MTX) clearance in patients. This work provides a general model for the rapid characterization of liver enhancers and identifies associations between enhancer variants and drug response.
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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.