CEACAM6 gene variants in inflammatory bowel disease

Publikation

CEACAM6 gene variants in inflammatory bowel disease

Wissenschaftlicher Artikel/Review - 29.04.2011

Glas Jürgen, Czamara Darina, Diegelmann Julia, Müller-Myhsok Bertram, Lohse Peter, Wolf Christiane, Ochsenkühn Thomas, Göke Burkhard, Lass Ulrich, Olszak Torsten, Beigel Florian, Weidinger Maria, Pfennig Simone, Tillack Cornelia, Fries Christoph, Seiderer Julia, Brand Stephan

Zitation

Glas J, Czamara D, Diegelmann J, Müller-Myhsok B, Lohse P, Wolf C, Ochsenkühn T, Göke B, Lass U, Olszak T, Beigel F, Weidinger M, Pfennig S, Tillack C, Fries C, Seiderer J, Brand S. CEACAM6 gene variants in inflammatory bowel disease. PloS one 2011; 6:e19319.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

PloS one 2011; 6

Veröffentlichungsdatum

29.04.2011

eISSN (Online)

1932-6203

Seiten

e19319

Kurzbeschreibung/Zielsetzung

BACKGROUND
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).

METHODOLOGY
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.

CONCLUSIONS
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.