ArticlePloS one2009
Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Impact of Promoter Polymorphisms on the Transcriptional Regulation of the Organic Cation Transporter OCT1 (SLC22A1).Journal of personalized medicine · 2018Article
- 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
- Genotypes of SLC22A4 and SLC22A5 regulatory loci are predictive of the response of chronic myeloid leukemia patients to imatinib treatment.Journal of experimental & clinical cancer research : CR · 2017Article
- Cellular Models and In Vitro Assays for the Screening of modulators of P-gp, MRP1 and BCRP.Molecules (Basel, Switzerland) · 2017Review
- Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors.The pharmacogenomics journal · 2016Article
- Changes in selective pressures associated with human population expansion may explain metabolic and immune related pathways enriched for signatures of positive selection.BMC genomics · 2016Article
- Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters.Clinical journal of the American Society of Nephrology : CJASN · 2015Article
- Genetic and epigenetic regulation of the organic cation transporter 3, SLC22A3.The pharmacogenomics journal · 2013Article
- Pharmacogene regulatory elements: from discovery to applications.Genome medicine · 2012Article
- Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters.Cell death & disease · 2011Article
- Functional characterization of liver enhancers that regulate drug-associated transporters.Clinical pharmacology and therapeutics · 2011Article
- Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases.Genes and immunity · 2011Article
- Pharmacogenomics of membrane transporters: past, present and future.Pharmacogenomics · 2010Article
- The pharmacogenomics of membrane transporters project: research at the interface of genomics and transporter pharmacology.Clinical pharmacology and therapeutics · 2010Review
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
Abstract
Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp) and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC) and Solute Carrier (SLC) superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi) was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.
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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.