Polymorphisms in the IkappaB-alpha promoter region and risk of diseases involving inflammation and fibrosis.
The transcription factor NFkappaB regulates inflammatory and other cellular responses. In non-stimulated cells, NFkappaB is linked to its inhibitor IkappaB, which plays a major role in controlling NFkappaB activity. Here, the gene promoter region of the major inducible IkappaB component (IkappaB-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 NFkappaB binding sites, kappaB2 and kappaB3, 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.
Mozzato-Chamay
N
N
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.
Corbett
E L
EL
Bailey
R L
RL
Mabey
D C
DC
Raynes
J
J
Conway
D J
DJ
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005714:Gambia / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D020672:I-kappa B Proteins; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012829:Silicosis / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D014141:Trachoma / Q000235:genetics*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha