title: Are inherited thrombotic risk factors associated with fibrostenosis in Crohn's disease?
abstract: BACKGROUND
  Fibrostenotic lesions are common complications in Crohn's disease (CD) often requiring surgery. Inherited thrombotic risk factors are associated with fibrosis in other chronic inflammatory diseases. The aim of the study was to assess whether inherited thrombotic risk factors are associated with fibrostenosis in CD.
  
  
  METHODS
  Clinical data on 529 CD patients were collected retrospectively. Subjects were tested for and grouped according to the presence of factor V Leiden (FVL), the prothrombin G20210A, and the methylenetetrahydrofolate reductase C677T mutation (MTHFR). Patients who underwent CD-related intestinal surgery were assessed for the presence of fibrostenosis, which was the primary endpoint. The diagnosis of fibrostenosis was based on surgical, pathological, and histopathological reports. A Cox proportional hazards model was used for statistical analysis.
  
  
  RESULTS
  Thirty-two (6.1%, heterozygous 30, homozygous 2) patients were carriers of FVL, 19 (3.6%, all heterozygous) carried the prothrombin variant, and 318 (60.1%) the MTHFR variant (243 heterozygous, 75 homozygous). In all, 303 (57.3%) patients underwent intestinal surgery. Fibrostenosis was identified in 219 (72.3%) surgical specimens. The rate of first intestinal surgeries with fibrostenosis tended to be more frequent in patients with the homozygous 677TT MTHFR mutation (hazard ratio, HR 1.39; 95% confidence interval [CI]: 0.98-1.97; P = 0.067). After adjustment for potential confounders homozygous 677TT MTHFR mutation did not remain a risk factor for intestinal surgery with fibrostenosis (HR 1.23; 95% CI: 0.77-1.98; P = 0.387). FVL and the prothrombin variant had no influence on the primary endpoint.
  
  
  CONCLUSIONS
  The MTHFR 677TT mutation, factor V Leiden, and the prothrombin G20210A mutation are not associated with fibrostenosis in CD.
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology; Vienna, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Novacek
authors.forename: Pavol
authors.initials: P
authors.lastname: Papay
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Miehsler
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lichtenberger
authors.forename: Raute
authors.initials: R
authors.lastname: Sunder-Plassmann
authors.forename: Harald
authors.initials: H
authors.lastname: Vogelsang
authors.forename: Cornelia
authors.initials: C
authors.lastname: Gratzer
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D003424:Crohn Disease / Q000150:complications* / Q000473:pathology / Q000601:surgery; D005165:Factor V / Q000235:genetics; D005260:Female; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011516:Prothrombin / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)