DLG5 variants in inflammatory bowel disease.
OBJECTIVE
Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD).


METHODS
Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test.


RESULTS
Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability.


CONCLUSIONS
We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD.
Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany.
Carsten
C
Büning
Lars
L
Geerdts
Thomas
T
Fiedler
Enno
E
Gentz
Ghyslaine
G
Pitre
Wolf
W
Reuter
Werner
W
Luck
Sabine
S
Buhner
Tomas
T
Molnar
Ferenc
F
Nagy
Janos
J
Lonovics
Axel
A
Dignass
Olfert
O
Landt
Renate
R
Nickel
Janine
J
Genschel
Herbert
H
Lochs
Hartmut H-J
HH
Schmidt
Heiko
H
Witt
D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000503:physiopathology; D003424:Crohn Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D006814:Hungary; D007413:Intestinal Mucosa / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D010539:Permeability; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C114461:DLG5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D025521:Tumor Suppressor Proteins