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Combined type-1 plasminogen activator inhibitor and NOD2/CARD15 genotyping predicts complicated Crohn's disease

M Alvarez-Lobos1, J I Arostegui, M Sans

  • 1Department of Gastroenterology, Hospital Clinic, CIBER-HEPAD, Barcelona, Spain.

Alimentary Pharmacology & Therapeutics
|February 3, 2007
PubMed

Insights

Genetic factors influence Crohn's disease behavior. Combining NOD2/CARD15 variants with the 4G/4G PAI-1 genotype predicts complicated Crohn's disease, suggesting a need for early interventions in at-risk patients.

Area of Science:

  • Gastroenterology
  • Genetics
  • Inflammatory Bowel Disease Research

Background:

  • NOD2/CARD15 gene variants are inconsistently linked to stricturing Crohn's disease.
  • Other genetic factors may influence disease behavior.

Purpose of the Study:

  • To investigate the combined effect of NOD2/CARD15 variants and the 4G/4G genotype of the type-1 plasminogen activator inhibitor (PAI-1) gene on Crohn's disease behavior.
  • To identify genetic predictors of disease complications.

Main Methods:

  • Prospective study of 170 Crohn's disease patients with a mean follow-up of 7 years.
  • Disease behavior classified using the Vienna classification and a non-hierarchical system.
  • Multivariate analysis to identify independent predictive factors for stricturing and penetrating behaviors.

Main Results:

  • Absence of colonic disease predicted stricturing behavior under Vienna criteria.
  • Ileal disease and combined NOD2/CARD15 variants with 4G/4G PAI-1 genotype predicted stricturing disease under non-hierarchical criteria.
  • 4G/4G PAI-1 genotype and male sex predicted penetrating behavior.

Conclusions:

  • Combined genotyping of PAI-1 and NOD2/CARD15 predicts complicated Crohn's disease.
  • Patients with these genetic variants may benefit from early therapeutic interventions.
Abstract

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