title: Relationship between methylation and colonic inflammation in inflammatory bowel disease.
abstract: OBJECTIVE
  To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients.
  
  
  METHODS
  We evaluated the methylation status of 2 genes (SLIT2 and TGFB2) in 226 biopsies taken from 62 colonoscopies of 38 patients (29 ulcerative colitis and 9 Crohn's colitis) using methylation-specific melting curve analysis. The relationships between methylation status and clinical, biological, endoscopic and histological activities were evaluated. Twenty-three of the 38 patients had a second colonoscopy and were included in a longitudinal analysis. Numerical results were given as the means ± SD of the sample and range, except when specified. Student t analysis, U Mann Whitney and ANOVA factor were used to compare the means. Qualitative results were based on the χ(2) test.
  
  
  RESULTS
  SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission (55% vs 18%, P < 0.001). SLIT2 methylation was also higher in samples with acute inflammation (56.5%) than in samples with chronic (24%) or absent inflammation (15%) (P < 0.001). For TGFB2 methylation, the correlation was only significant with endoscopic activity. Methylation was higher in the distal colon for both genes (P < 0.001 for SLIT2 and P = 0.022 for TGFB2). In the multivariate analysis, only inflammation status (and not disease duration or extension) was independently associated with SLIT2 methylation [OR = 6.6 (95%CI: 1.65-27.36), P = 0.009]. In the longitudinal analysis, the maintenance of endoscopic remission was protective for methylation.
  
  
  CONCLUSIONS
  Endoscopic and histological inflammation are predictive for SLIT2 methylation.
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Triana
authors.initials: T
authors.lastname: Lobatón
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Azuara
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodríguez-Moranta
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Loayza
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanjuan
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: de Oca
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Robles
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Guardiola
authors.affiliation: Triana Lobatón, Francisco Rodríguez-Moranta, Jordi Guardiola, Department of Gastroenterology, University Hospital of Bellvitge, IDIBELL, Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003106:Colon / Q000473:pathology; D003113:Colonoscopy; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019175:DNA Methylation; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D053781:Transforming Growth Factor beta2 / Q000235:genetics*; D016896:Treatment Outcome; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2; D000098552:Slit Homolog 2 Protein
keywords: Aberrant methylation; Colitis associated colorectal cancer; Colonic inflammation; Dysplasia; Inflammatory bowel disease