CEACAM6 gene variants in inflammatory bowel disease.

The carcinoembryonic antigen-related cell adhesion molecule 6
(CEACAM6) acts as a receptor for adherent-invasive 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). In this
study, a total of 2,683 genomic DNA samples (including DNA from 858
CD patients, 475 patients with ulcerative colitis (UC), and 1,350
healthy, unrelated controls) was analyzed for eight CEACAM6 SNPs
(rs10415946, rs1805223 = p.Pro42Pro, rs4803507, rs4803508,
rs11548735 = p.Gly239Val, rs7246116 = pHis260His, rs2701,
rs10416839). In addition, a detailed haplotype analysis and
genotype-phenotype analysis were performed. Overall, our genotype
analysis did not reveal any significant association of the
investigated CEACAM6 SNPs and haplotypes with CD or UC
susceptibility, although certain CEACAM6 SNPs modulated CEACAM6
expression in intestinal epithelial cell lines. Despite its
function as receptor of AIEC in ileal CD, we found no association
of the CEACAM6 SNPs with ileal or ileocolonic CD. Moreover, there
was no evidence of epistasis between the analyzed CEACAM6 variants
and the main CD-associated NOD2, IL23R and ATG16L1 variants. This
study represents the first detailed analysis of CEACAM6 variants in
IBD patients. Despite its important role in bacterial attachment in
ileal CD, we could not demonstrate a role for CEACAM6 variants in
IBD susceptibility or regarding an ileal CD phenotype. Further
functional studies are required to analyze if these gene variants
modulate ileal bacterial attachment.