These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease.
In a Spanish population from Madrid, mutations of the NOD2/CARD15 gene were a marker of susceptibility to Crohn disease and were associated with ileal disease.
We show a significant association of ileal involvement with CARD15 variants (OR = 1.8; p = 0.02), HLA-DRB1*0701 (OR = 1.9; p = 0.006) and DRB1*04 (OR = 1.7; p = 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients.
We show a significant association of ileal involvement with CARD15 variants (OR = 1.8; p = 0.02), HLA-DRB1*0701 (OR = 1.9; p = 0.006) and DRB1*04 (OR = 1.7; p = 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients.
We show a significant association of ileal involvement with CARD15 variants (OR = 1.8; p = 0.02), HLA-DRB1*0701 (OR = 1.9; p = 0.006) and DRB1*04 (OR = 1.7; p = 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients.
NOD2/CARD15 was associated with ileal involvement, while presence of TNF-863A was inversely associated with ileal disease (OR = 0.42, p= 0.008) and positively associated with isolated colitis (OR = 2.16, p= 0.008, OR = 2.12, p= 0.03 corrected) and familial disease (p= 0.004).
NOD2/CARD15 was associated with ileal involvement, while presence of TNF-863A was inversely associated with ileal disease (OR = 0.42, p= 0.008) and positively associated with isolated colitis (OR = 2.16, p= 0.008, OR = 2.12, p= 0.03 corrected) and familial disease (p= 0.004).
The association of the SLC22A -TC haplotype and CARD15 alleles with ileal disease suggests that these variants have biologically intertwined effects in the pathogenesis of CD.
These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients.
These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients.
Genotype-phenotype analysis demonstrated that CARD15 variants were associated with ileal disease (p=0.0006, OR = 9.3, CI = 2.2-34) and protective for colonic CD (p = 0.01, OR = 0.18).
NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies.
The ASCA titer (odds ratio (OR): 2.7 per 25 U, 95% confidence interval (CI): 1.5-46.7) and ileal disease were associated with stricturing/penetrating behavior, independently of NOD2/CARD15 status.
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.
The levels of Tcf-4 mRNA were decreased in patients with ileal disease irrespective of degree of inflammation, but were not decreased in colonic CD or ulcerative colitis.
The levels of Tcf-4 mRNA were decreased in patients with ileal disease irrespective of degree of inflammation, but were not decreased in colonic CD or ulcerative colitis.