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 journalArticle

Abstract

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
Volume28
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

Fingerprint

African Americans
Blood Vessels
Haplotypes
Population
Binding Sites
Chromatin Immunoprecipitation
Computational Biology
Multiple Myeloma
Mitogens
Gene Frequency
Single Nucleotide Polymorphism
Transfection
Transcription Factors
Asthma
Nucleotides

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Idelman, G., Taylor, J. G., Tongbai, R., Chen, R. A., Haggerty, C. M., Bilke, S., ... Gardner, K. (2007). Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations. Human Mutation, 28(8), 824-829. https://doi.org/10.1002/humu.20523

Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations. / Idelman, Gila; Taylor, James G.; Tongbai, Ron; Chen, Renee A.; Haggerty, Cynthia M.; Bilke, Sven; Chanock, Stephen J.; Gardner, Kevin.

In: Human Mutation, Vol. 28, No. 8, 08.2007, p. 824-829.

Research output: Contribution to journalArticle

Idelman, G, Taylor, JG, Tongbai, R, Chen, RA, Haggerty, CM, Bilke, S, Chanock, SJ & Gardner, K 2007, 'Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations', Human Mutation, vol. 28, no. 8, pp. 824-829. https://doi.org/10.1002/humu.20523
Idelman, Gila ; Taylor, James G. ; Tongbai, Ron ; Chen, Renee A. ; Haggerty, Cynthia M. ; Bilke, Sven ; Chanock, Stephen J. ; Gardner, Kevin. / Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations. In: Human Mutation. 2007 ; Vol. 28, No. 8. pp. 824-829.
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