Discovery of regulatory elements in human ATP-binding cassette transporters through expression quantitative trait mapping

Pharmacogenomics J. 2012 Jun;12(3):214-26. doi: 10.1038/tpj.2011.8. Epub 2011 Mar 8.


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 single-nucleotide polymorphisms may affect disease susceptibility and response to drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Cell Line, Tumor
  • Continental Population Groups / genetics
  • Databases, Nucleic Acid
  • Female
  • Gene Expression Regulation
  • Genes, Reporter
  • Genotype
  • Humans
  • Least-Squares Analysis
  • Linear Models
  • Male
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Regulatory Elements, Transcriptional*
  • Sex Factors
  • Transcription, Genetic
  • Transfection


  • ATP-Binding Cassette Transporters