Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping

Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping

ATP-Binding Cassette (ABC) membrane transporters determine the disposition of many drugs, metabolites and endogenous compounds. Coding region variation in ABC transporters is the cause of many genetic disorders, but much less is known about the genetic basis and functional outcome of ABC transporter...

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Main Authors: Matsson, Pär, Yee, Sook Wah, Markova, Svetlana, Morrissey, Kari, Jenkins, Gerard, Xuan, Jiekun, Jorgenson, Eric, Kroetz, Deanna L., Giacomini, Kathleen M.
Format: Online
Language:English
Published: 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325368/
id pubmed-3325368
recordtype oai_dc
spelling pubmed-33253682012-12-01 Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping Matsson, Pär Yee, Sook Wah Markova, Svetlana Morrissey, Kari Jenkins, Gerard Xuan, Jiekun Jorgenson, Eric Kroetz, Deanna L. Giacomini, Kathleen M. Article ATP-Binding Cassette (ABC) membrane transporters determine the disposition of many drugs, metabolites and endogenous compounds. Coding region variation in ABC transporters is the cause of many genetic disorders, but much less is known about the genetic basis and functional outcome of ABC transporter expression level variation. We used genotype and mRNA transcript level data from human lymphoblastoid cell lines to assess population and gender differences in ABC transporter expression, and to guide the discovery of genomic regions involved in transcriptional regulation. Nineteen of 49 ABC genes were differentially expressed between individuals of African, Asian and European descent suggesting an important influence of race on expression level of ABC transporters. Twenty-four significant associations were found between transporter transcript levels and proximally located genetic variants. Several of the associations were experimentally validated in reporter assays. Through influencing ABC expression levels, these SNPs may affect disease susceptibility and response to drugs. 2011-03-08 2012-06 /pmc/articles/PMC3325368/ /pubmed/21383772 http://dx.doi.org/10.1038/tpj.2011.8 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Matsson, Pär
Yee, Sook Wah
Markova, Svetlana
Morrissey, Kari
Jenkins, Gerard
Xuan, Jiekun
Jorgenson, Eric
Kroetz, Deanna L.
Giacomini, Kathleen M.
spellingShingle Matsson, Pär
Yee, Sook Wah
Markova, Svetlana
Morrissey, Kari
Jenkins, Gerard
Xuan, Jiekun
Jorgenson, Eric
Kroetz, Deanna L.
Giacomini, Kathleen M.
Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping
author_facet Matsson, Pär
Yee, Sook Wah
Markova, Svetlana
Morrissey, Kari
Jenkins, Gerard
Xuan, Jiekun
Jorgenson, Eric
Kroetz, Deanna L.
Giacomini, Kathleen M.
author_sort Matsson, Pär
title Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping
title_short Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping
title_full Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping
title_fullStr Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping
title_full_unstemmed Discovery of Regulatory Elements in Human ATP-Binding Cassette Transporters through Expression Quantitative Trait Mapping
title_sort discovery of regulatory elements in human atp-binding cassette transporters through expression quantitative trait mapping
description ATP-Binding Cassette (ABC) membrane transporters determine the disposition of many drugs, metabolites and endogenous compounds. Coding region variation in ABC transporters is the cause of many genetic disorders, but much less is known about the genetic basis and functional outcome of ABC transporter expression level variation. We used genotype and mRNA transcript level data from human lymphoblastoid cell lines to assess population and gender differences in ABC transporter expression, and to guide the discovery of genomic regions involved in transcriptional regulation. Nineteen of 49 ABC genes were differentially expressed between individuals of African, Asian and European descent suggesting an important influence of race on expression level of ABC transporters. Twenty-four significant associations were found between transporter transcript levels and proximally located genetic variants. Several of the associations were experimentally validated in reporter assays. Through influencing ABC expression levels, these SNPs may affect disease susceptibility and response to drugs.
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325368/
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