title: Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer.
abstract: BACKGROUND
  Health disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA).
  
  
  METHODS
  From self-identified, healthy, 20 to 29-year-old AA (n = 21) and CA (n = 17), we established cultures of blood outgrowth endothelial cells (BOEC) and applied microarray profiling. BOEC have never been exposed to in vivo influences, and their gene expression reflects culture conditions (meticulously controlled) and donor genetics. Significance Analysis of Microarray identified differential expression of single genes. Gene Set Enrichment Analysis examined expression of pre-determined gene sets that survey nine biological systems relevant to endothelial biology.
  
  
  RESULTS
  At the highly stringent threshold of False Discovery Rate (FDR) = 0, 31 single genes were differentially expressed in AA. PSPH exhibited the greatest fold-change (AA > CA), but this was entirely accounted for by a homolog (PSPHL) hidden within the PSPH probe set. Among other significantly different genes were: for AA > CA, SOS1, AMFR, FGFR3; and for AA < CA, ARVCF, BIN3, EIF4B. Many more (221 transcripts for 204 genes) were differentially expressed at the less stringent threshold of FDR <.05. Using the biological systems approach, we identified shear response biology as being significantly different for AA versus CA, showing an apparent tonic increase of expression (AA > CA) for 46/157 genes within that system.
  
  
  CONCLUSIONS
  Many of the genes implicated here have substantial roles in endothelial biology. Shear stress response, a critical regulator of endothelial function and vascular homeostasis, may be different between AA and CA. These results potentially have direct implications for the role of endothelial cells in vascular disease (hypertension, stroke) and cancer (via angiogenesis). Also, they are consistent with our over-arching hypothesis that genetic influences stemming from ancestral continent-of-origin could impact upon endothelial cell biology and thereby contribute to disparity of vascular-related disease burden among AA. The method used here could be productively employed to bridge the gap between information from structural genomics (for example, disease association) and cell function and pathophysiology.
authors.affiliation: Vascular Biology Center, Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wei
authors.forename: L C
authors.initials: LC
authors.lastname: Milbauer
authors.forename: J
authors.initials: J
authors.lastname: Enenstein
authors.forename: J
authors.initials: J
authors.lastname: Nguyen
authors.forename: W
authors.initials: W
authors.lastname: Pan
authors.forename: R P
authors.initials: RP
authors.lastname: Hebbel
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D014652:Vascular Diseases / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase