Combined type-1 plasminogen activator inhibitor and NOD2/CARD15 genotyping predicts complicated Crohn's disease behaviour.
BACKGROUND
NOD2/CARD15 gene variants have not been universally associated with stricturing behaviour in Crohn's disease. Other behaviour modifying genes could explain these results.


OBJECTIVE
To study the combined influence of NOD2/CARD15 variants and 4G/4G genotype of type-1 plasminogen activator inhibitor (PAI-1) gene on Crohn's disease behaviour.


METHODS
One hundred and seventy Crohn's disease patients were studied prospectively, with a mean follow-up of 7+/- 6 years. Disease behaviour was registered by using two criteria: the Vienna classification and a non-hierarchical classification based on the behavioural Vienna categories.


RESULTS
In the multivariate analysis for stricturing behaviour according to the Vienna categories, only absence of colonic disease (OR, 4.0; 95% CI: 1.49-11.1; P = 0.006) was an independent predictive factor. However, in the multivariate analysis for stricturing disease applying a non-hierarchical criteria, ileal disease (OR, 4.19; 95% CI: 1.30-13.5; P = 0.01), and carrying both NOD2/CARD15 variants and the 4G/4G PAI-1 genotype (OR, 5.02; 95% CI: 1.44-17.48; P = 0.01) were independent predictive factors. In the multivariate analysis for penetrating behaviour, the 4G/4G PAI-1 (OR, 3.10; 95% CI: 1.54-6.23; P = 0.001) and male sex (OR, 2.44; 95% CI: 1.30-4.60; P = 0.005) were independent predictive factors irrespective of criteria applied.


CONCLUSIONS
Combined PAI-1 and NOD2/CARD15 genotyping predict complicated Crohn's disease. Patients with these variants could benefit from early interventions.
Alvarez-Lobos
M
M
Department of Gastroenterology, Hospital Clinic, CIBER-HEPAD, Barcelona, Spain.
Arostegui
J I
JI
Sans
M
M
Tassies
D
D
Piu
J
J
Reverter
J C
JC
Pique
J M
JM
Yagüe
J
J
Panés
J
J
D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D017395:Plasminogen Activator Inhibitor 1