Abstract
BackgroundThe 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).MethodologyIn 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.ConclusionsThis 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.
Highlights
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD), characterized by an aberrant mucosal immune response to bacteria-derived antigens in the gut of genetically susceptible hosts [1,2]
Despite its important role in bacterial attachment in ileal CD, we could not demonstrate a role for carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) variants in IBD susceptibility or regarding an ileal CD phenotype
This hypothesis is strengthened by data from genetic association studies identifying CD susceptibility genes involved in innate immunity and bacterial recognition (NOD2/CARD15) [10,11], and from genomewide association studies (GWAS), which identified susceptibility genes involved in autophagy (ATG16L1, IRGM) [4,5] and the proinflammatory IL-23/Th17 pathway [12]
Summary
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD), characterized by an aberrant mucosal immune response to bacteria-derived antigens in the gut of genetically susceptible hosts [1,2]. The exact pathogenesis of IBD still remains unsolved, current evidence indicates that defective T-cell apoptosis [3] and autophagy [4,5,6,7] as well as an impairment of intestinal epithelial barrier function [8,9] play important roles This hypothesis is strengthened by data from genetic association studies identifying CD susceptibility genes involved in innate immunity and bacterial recognition (NOD2/CARD15) [10,11], and from genomewide association studies (GWAS), which identified susceptibility genes involved in autophagy (ATG16L1, IRGM) [4,5] and the proinflammatory IL-23/Th17 pathway [12]. 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)
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