CEACAM6 gene variants in inflammatory bowel disease

Abstract

Background: The carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) acts as a receptor for adherentinvasive E. coli (AIEC) and its ileal expression is increased in patients with Crohn's disease (CD). Given its contribution to the pathogenesis of CD, we aimed to investigate the role of genetic variants in the CEACAM6 region in patients with inflammatory bowel diseases (IBD).

Diet-induced hypoxia responsive element demethylation increases CEACAM6 expression, favouring Crohn's disease-associatedEscherichia colicolonisation

“…To date, no study has investigated the molecular mechanisms that could lead to abnormal expression of the CEACAM6 gene, which encodes an AIEC receptor, in the ileal mucosa of patients with CD. A recent study analysing a large number of patients and controls did not reveal a role for common genetic variants of CEACAM6 in IBD susceptibility or in an ileal CD phenotype 15. The aetiology of IBD is only partially explained by the current genetic risk map.…”

“…However, abnormal CEACAM6 expression in CD remains poorly understood. Abnormal expression of CEACAM6 cannot be explained by germline genetic alteration because genome-wide association studies (GWAS) and locus-specific analysis did not reveal single-nucleotide polymorphisms (SNPs) in the CEACAM6 gene or promoter associated with IBD 15 . CEACAM6 gene expression can be triggered by different transcriptions factors in cooperation with specific epigenetic marks that could be deregulated in an inflammatory context.…”

Ulcerative Colitis

“…They are found in the terminal ileum of about a quarter of patients with CD but generally not in UC patients, and can also be found in the ilea of some non-IBD patients; the latter indicates that their presence is not strictly related to IBD (Darfeuille-Michaud et al, 2004;Pineton de Chambrun et al, 2008). The adherent and invasive properties of AIEC suggest that they may be initiators of inflammation in CD, but it is more likely that they aggravate CD inflammation caused by a more fundamental defect (Glas et al, 2011). This follows from the fact that there is little evidence that AIEC penetrate into the lamina propria of CD patients without a preexisting break in the mucosa (cause by preexisting inflammation) and that their colonization of the epithelium appears to result from inflammation-induced up-regulation of CEACAM6.…”