title: CEACAM6 gene variants in inflammatory bowel disease.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine II-Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Christoph
authors.initials: C
authors.lastname: Fries
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tillack
authors.forename: Simone
authors.initials: S
authors.lastname: Pfennig
authors.forename: Maria
authors.initials: M
authors.lastname: Weidinger
authors.forename: Florian
authors.initials: F
authors.lastname: Beigel
authors.forename: Torsten
authors.initials: T
authors.lastname: Olszak
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lass
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolf
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Julia
authors.initials: J
authors.lastname: Diegelmann
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D001422:Bacterial Adhesion; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D002648:Child; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000502:physiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA
chemical_list: D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D004247:DNA