We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD.
Indeed, a diminished activity of transforming growth factor-β1, as indicated by a reduced phosphorylation of Smad3, a signalling molecule associated with the activated transforming growth factor-β receptor, is evident in the inflamed gut of inflammatory bowel disease patients and this alteration is due to high Smad7, an intracellular inhibitor of Smad3 phosphorylation.
Consistent with epidemiologic predictions, many IBD-associated loci demonstrate genome-wide significant associations to both CD and UC, notably, genes whose products function in the interleukin-23 pathway, and transcription factors, including NK2 transcription factor related, locus 3 (NKX2-3), SMAD3, STAT3, ZMIZ1, and c-REL.