The study suggests that SNPs (T>C substitution) affect the function of the DLG5 protein and thus play a role in the development of IBD, in particular Crohn's disease.
Since the roles of DLG5 in inflammatory bowel disease (IBD) and Crohn's disease (CD) have been reviewed, here, our review focuses on the roles of DLG5 in epithelial cell polarity maintenance and cancer development.
In this study, we examined the genetic association of another DLG5 SNP rs2289310" genes_norm="9231">P1371Q (rs2289310) with IBD and its interaction with R30Q in disease susceptibility.
The single-nucleotide polymorphisms (SNPs) -1237T/C (rs5743836) and 2848A/G (rs352140=p.Pro545Pro) in TLR9, the main CD-associated variants within the genes for NOD2, IL23R, ATG16L1, and variants in the IBD5 locus and in the DLG5 gene were assessed in 956 patients with IBD (606 CD and 350 ulcerative colitis) and in 792 healthy controls.
Discs large homolog 5 (DLG5), a member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, has been associated with Crohn's disease (CD), but its role in the pathogenesis of this inflammatory bowel disease is disputed.
Polymorphisms R702W, G908R, and 3020insC of CARD15 (caspase activating recruitment domain 15); Asp299Gly and Thr399Ile of TLR4; -207G-->C, 1672C-->T (L503F), rs3792876, rs274551, rs272893, and rs273900 of SLC22A4/5; and 113G-->A as well as rs2289311, rs1270912, and rs2165047 of DLG5 (Drosophila discs large homologue 5) were assessed in 103 pediatric-onset and 696 adult-onset IBD patients.
This study provides some evidence that DLG5 haplotype A is associated with reduced risk of IBD in the New Zealand Caucasian population, but this association will need to be replicated in an independent sample.
A significant association between the DLG5 variant (R30Q) and inflammatory bowel disease (IBD) has been confirmed in several independent adult IBD cohorts.
This study provides some evidence that DLG5 haplotype A is associated with reduced risk of IBD in the New Zealand Caucasian population, but this association will need to be replicated in an independent sample.
The R30Q variant in the DLG5 gene does not appear to be associated with an overall increase in the risk of disease in a British IBD cohort, but differences in its frequency in subgroups of CD patients warrant further investigation.
To date, three loci have been validated to confer susceptibility to inflammatory bowel disease (IBD): the CARD15/NOD2 gene, the discs large homolog 5 gene (DLG5), and the IBD5 locus on 5q31 (IBD5).
We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort).
Together, the results indicate a role for DLG5 variants in IBD susceptibility and suggest that further studies are warranted to evaluate this role in different IBD populations and to determine the functional pathways that couple DLG5 variants to IBD.
A major role in adult Crohn's disease (CD) has been defined for 3 polymorphisms in the CARD15 gene, whereas variants in the SLC22A4, SLC22A5, and DLG5 genes could have a minor contribution to IBD susceptibility.
In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5R30Q variant in Hungarian IBD patients.
Together, the results indicate a role for DLG5 variants in IBD susceptibility and suggest that further studies are warranted to evaluate this role in different IBD populations and to determine the functional pathways that couple DLG5 variants to IBD.