Lack of association of the 3'-UTR polymorphism in the NFKBIA gene with Crohn's disease in an Israeli cohort.
BACKGROUND
Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract associated with dysregulation of the immune response. It is caused by a combination of environmental and genetic factors. Patients with CD have a TH1-type inflammatory response characterized by nuclear factor kappa B (NFkappaB) activation. Mutations in the bacterial pattern recognition receptors NOD2/CARD15 and Toll-like receptor 4 (TLR4) genes, which lead to activation of NFkappaB under normal circumstances, have been associated with increased susceptibility for CD. NFkappaB plays a critical role in the immune response and is down-regulated by NFkappaB inhibitor alpha (NFKBIA). NFKBIA was found to be a susceptibility gene for German CD patients lacking NOD2/CARD15 mutations.


METHODS
A cohort of 231 Israeli CD patients previously genotyped for the single nucleotide polymorphisms (SNPs) in the CARD15, TLR4 susceptibility genes for CD, was analyzed for the 3'-untranslated region (UTR) SNP of the NFKBIA gene in comparison to 100 healthy ethnically matched controls. We evaluated the contribution of the 3'-UTR SNP in NFKBIA in patients with or without other SNPs in CARD15 to age of onset, disease location, and disease behavior (Vienna classification).


RESULTS
We did not identify a significant difference in allele and genotype frequencies between either groups or an effect on phenotype. No interactions were found between NFKBIA and any NOD2.


CONCLUSIONS
The contribution of population diversity to susceptibility genes for CD plays an important role in disease-associated variants and is important for better understanding of the pathologic mechanisms of the polymorphism.
Leshinsky-Silver
E
E
Molecular Genetics Lab, E Wolfson Medical Center, POB 5, Holon, Israel, 58100. leshinsky@wolfson.health.gov.il
Karban
A
A
Cohen
S
S
Fridlander
M
M
Davidowich
O
O
Kimmel
G
G
Shamir
R
R
Levine
A
A
D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D015331:Cohort Studies; D003424:Crohn Disease / Q000208:ethnology* / Q000235:genetics*; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000208:ethnology; D016328:NF-kappa B / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; D016328:NF-kappa B; C120111:NFKBIL1 protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein