A polymorphism of the NFKBIA gene is associated with Crohn's disease patients lacking a predisposing allele of the CARD15 gene.
OBJECTIVE
Nuclear factor kappa-B (NFkappaB) plays a crucial role in diseases associated with dysregulated immune response. NFkappaB inhibitor alpha downregulates the activity of NFkappaB.


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.


CONCLUSIONS
The findings indicate that the phenotype Crohn's disease is to be substructured with respect to genetic susceptibility.
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C120111:NFKBIL1 protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein