title: A GA microsatellite in the Fli1 promoter modulates gene expression and is associated with systemic lupus erythematosus patients without nephritis.
abstract: BACKGROUND
  The transcription factor Fli1 is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Recently, a GA(n) polymorphic microsatellite was characterized in the mouse Fli1 promoter that modulates promoter activity and is truncated in two lupus mouse models compared to non-autoimmune prone mice. In this work, we characterize a homologous GA(n) microsatellite in the human Fli1 promoter. The purpose of this study is to determine the effect of the microsatellite length on Fli1 promoter activity in vitro and to determine if the length of the GA(n) microsatellite is associated with SLE and/or specific disease characteristics.
  
  
  METHODS
  Constructs with variable lengths of the GA(n) microsatellite in the Fli1 promoter were generated and analyzed in promoter/reporter (P/R) assays in a human T cell line. Using three SLE patient cohorts and matched controls, microsatellite length was measured and association with the presence of disease and the occurrence of specific disease manifestations was assessed.
  
  
  RESULTS
  P/R assays demonstrated that the presence of a shorter microsatellite resulted in higher Fli1 promoter activity. A significant association was observed in the lupus cohort SLE in Gullah Health (SLEIGH) between the GA(26) base pair allele and absence of nephritis.
  
  
  CONCLUSIONS
  This study demonstrates that a GA(n) microsatellite in the human Fli1 promoter is highly polymorphic. The length of the microsatellite is inversely correlated to Fli1 promoter activity in a human T cell line. Although no association between microsatellite length and lupus was observed, an association between a specific microsatellite length and patients without nephritis in the SLEIGH cohort was observed.
authors.affiliation: Division of Rheumatology, Department of Medicine, Medical University of South Carolina, 96 Jonathon Lucas St, Charleston, SC 29425, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Morris
authors.forename: May Y
authors.initials: MY
authors.lastname: Amria
authors.forename: Emily
authors.initials: E
authors.lastname: Kistner-Griffin
authors.forename: John L
authors.initials: JL
authors.lastname: Svenson
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Nowling
mesh_terms: D015870:Gene Expression; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics*; D014162:Transfection
chemical_list: C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1