Polymorphisms in the IκB-α promoter region and risk of diseases involving inflammation and fibrosis

The transcription factor NF kappaB regulates inflammatory and other cellular responses. In non-stimulated cells, NF kappaB is linked to its inhibitor I kappaB, which plays a major role in controlling NF kappaB activity. Here, the gene promoter region of the major inducible I kappaB component (I kappaB-alpha) was studied to identify single nucleotide polymorphisms (SNPs), and to test if these are associated with risk of two diseases involving inflammation and fibrosis (trachoma and silicosis). Three SNPs were identified at positions -881, -826 and -297 relative to the transcription start site. The position -297 is close to two NF kappaB binding sites, kappa B2 and kappa B3, but the alleles were not associated with either disease. Alleles at positions -881 and -826 were in complete linkage disequilibrium with each other, and the rare haplotype was significantly less frequent among patients with trachoma compared to controls, although there was no difference in frequencies between silicosis patients and controls.