title: The 4G/4G genotype of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene is a determinant of penetrating behaviour in patients with Crohn's disease.
abstract: BACKGROUND
  Crohn's disease is a heterogeneous disorder with polygenic inheritance.
  
  
  OBJECTIVE
  To assess the effect of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene, the major inhibitor of fibrinolysis, on Crohn's disease susceptibility and phenotype.
  
  
  METHODS
  One hundred and fifty-seven patients with Crohn's disease and 350 controls were included prospectively. Medical records were reviewed to determine changes in the Crohn's disease phenotype. The 4G/5G polymorphism was assessed by polymerase chain reaction techniques.
  
  
  RESULTS
  The frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes were similar in patients with Crohn's disease and controls. The 4G/4G genotype (P < 0.0001; odds ratio, 4.84) and male sex (P = 0.009; odds ratio, 2.63) were independent risk factors for penetrating behaviour in Crohn's disease. Most Crohn's disease patients had a non-penetrating phenotype at diagnosis. The probability of development of a penetrating phenotype within 5 years of diagnosis was higher in patients with the 4G/4G genotype (72% vs. 19%, P < 0.0001).
  
  
  CONCLUSIONS
  The 4G/4G genotype of the PAI-1 gene does not influence Crohn's disease susceptibility, but increases by five-fold the probability of penetrating behaviour. Most patients with the 4G/4G genotype have a non-penetrating phenotype at diagnosis, but develop a penetrating behaviour within 5 years. Genotyping the 4G/5G polymorphism may be useful for the identification of a sub-group of patients with aggressive Crohn's disease, who might benefit from specific therapy.
authors.affiliation: Department of Gastroenterology, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sans
authors.forename: D
authors.initials: D
authors.lastname: Tàssies
authors.forename: M
authors.initials: M
authors.lastname: Pellisé
authors.forename: G
authors.initials: G
authors.lastname: Espinosa
authors.forename: L
authors.initials: L
authors.lastname: Quintó
authors.forename: J M
authors.initials: JM
authors.lastname: Piqué
authors.forename: J C
authors.initials: JC
authors.lastname: Reverter
authors.forename: J
authors.initials: J
authors.lastname: Panés
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D017395:Plasminogen Activator Inhibitor 1