Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations

Gila Idelman, James G. Taylor, Ron Tongbai, Renee A. Chen, Cynthia M. Haggerty, Sven Bilke, Stephen J. Chanock, Kevin Gardner

Research output: Contribution to journalArticlepeer-review


Multiple variants of the vascular adhesion molecule-1 (VCAM1) promoter show increased nucleotide heterozygosity in the African American population. Using a novel transfection-based transcriptional pathway profiling method, we show that select uncommon variants are functionally hyperactive. Eight candidate VCAM1 promoter haplotypes comprising 13 previously identified SNPs were assessed for response to known mitogens. Activity was correlated with bioinformatic analysis of hyper- and hyporesponsive variants to identify the gain or loss of haplotype-specific transcription factor binding site (TFBS). Using this approach, a low frequency regulatory allele (c.-540A>G; dbSNP rs3783605:A>G), found in a hyperactive VCAM1 promoter haplotype, was shown to create a candidate binding site for ETS2 that was confirmed in vivo by chromatin immunoprecipitation. This report provides the first functional evaluation of VCAM1 promoter polymorphisms and establishes a hypothetical foundation for investigation of their role in the pathogenesis of VCAM1-associated diseases that disproportionately afflict African Americans, including thromboembolic diseases, asthma, and multiple myeloma.

Original languageEnglish (US)
Pages (from-to)824-829
Number of pages6
JournalHuman mutation
Issue number8
StatePublished - Aug 2007


  • African American populations
  • Bioinformatics
  • Promoter
  • Regulatory SNPs
  • SNP
  • VCAM1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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