title: T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease.
abstract: BACKGROUND
  The T-cell activation Rho GTPase-activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location.
  
  
  METHODS
  Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results.
  
  
  RESULTS
  Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049).
  
  
  CONCLUSIONS
  Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.
authors.affiliation: Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Connelly
authors.affiliation: Department of Biostatistics, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Berg
authors.affiliation: Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Harris
authors.affiliation: Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.affiliation: Department of Pathology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Ruggiero
authors.affiliation: Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Deiling
authors.affiliation: Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: David L
authors.initials: DL
authors.lastname: Brinton
authors.affiliation: Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania. Electronic address: wkoltun@hmc.psu.edu.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Koltun
mesh_terms: D000293:Adolescent; D000328:Adult; D001004:Anus Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D012809:Colon, Sigmoid / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008297:Male; D010641:Phenotype; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D020690:GTPase-Activating Proteins; C557017:TAGAP protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Colonic mRNA expression; Crohn's disease; Inflammation; Inflammatory bowel disease; Surgery; Surgical genetics; TAGAP; rs212388