title: The influence of CTGF single-nucleotide polymorphisms on outcomes in Crohn's disease.
abstract: OBJECTIVE
  To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease.
  
  
  BACKGROUND
  The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes.
  
  
  METHODS
  DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698, and rs9399005), which modulate nuclear factor binding and CTGF production, and a smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped using the Montreal Disease Classification.
  
  
  RESULTS
  Sixty-seven of 147 patients (45.6%) were male; the mean age at diagnosis was 30.3 ± 12.6 years and the mean follow-up duration was 8.3 ± 7.1 years. Genotype-phenotype analysis demonstrated that the rs6918698GG genotype was associated with an older age of disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144-0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of Crohn's disease after intestinal resection. On multivariate analysis, male sex odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617; P = 0.005) of surgical recurrence.
  
  
  CONCLUSIONS
  These data implicate the rs6918698GG genotype with an age of disease onset of greater than 40 years in Crohn's disease whereas the rs9402373CC genotype is associated with a nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the rate of recurrence after terminal ileal resection for Crohn's disease.
authors.affiliation: *Department of Colorectal Surgery †Centre for Colorectal Disease ‡Department of Gastroenterology §Department of Pathology, St Vincent's University Hospital and School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: John P
authors.initials: JP
authors.lastname: Burke
authors.forename: Robert M
authors.initials: RM
authors.lastname: O'Connell
authors.forename: Grainne
authors.initials: G
authors.lastname: Lennon
authors.forename: Glen A
authors.initials: GA
authors.lastname: Doherty
authors.forename: Denise
authors.initials: D
authors.lastname: Keegan
authors.forename: Diarmuid
authors.initials: D
authors.lastname: O'Donoghue
authors.forename: Hugh
authors.initials: H
authors.lastname: Mulcahy
authors.forename: John
authors.initials: J
authors.lastname: Hyland
authors.forename: Desmond C
authors.initials: DC
authors.lastname: Winter
authors.forename: Kieran
authors.initials: K
authors.lastname: Sheahan
authors.forename: P Ronan
authors.initials: PR
authors.lastname: O'Connell
mesh_terms: D000328:Adult; D017668:Age of Onset; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics* / Q000601:surgery*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012189:Retrospective Studies; D051900:Smad3 Protein / Q000235:genetics
chemical_list: C526317:CCN2 protein, human; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D055513:Connective Tissue Growth Factor