Background and aims: Nuclear factor kappa-B (NFkappaB) plays a crucial role in diseases associated with dysregulated immune response. NFkappaB inhibitor alpha downregulates the activity of NFkappaB.
Patients and methods: To evaluate the contribution of the NFkappaB inhibitor alpha gene in Crohn's disease single nucleotide polymorphisms in the 3'-UTR and at position -420 in the promoter were studied in 259 patients with Crohn's disease genotyped for the variations of the CARD15 gene in comparison to 441 healthy controls. Additionally we screened the coding region of the NFkappaB inhibitor alpha gene for polymorphisms by SSCP analysis.
Results: In comparison to controls the A allele and the AA genotype frequencies of the single nucleotide polymorphisms in the 3'-UTR were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene. Similarly, the difference between patients harboring no predisposing CARD15 alleles and patients harboring such a variation was significant.
Conclusion: The findings indicate that the phenotype Crohn's disease is to be substructured with respect to genetic susceptibility.