Investigation of association of the DLG5 gene with phenotypes of inflammatory bowel disease in the British population.

BACKGROUND AND AIMS: Mutations in the DLG5 gene are associated with an increased risk of inflammatory bowel disease (IBD) in some European populations. Initial investigation of a British IBD population showed evidence of association of one of three DLG5 variants, R30Q, in a family-based collection but not in a case-control cohort. We have now examined the association of the R30Q polymorphism in a large cohort of British IBD cases, tested for interaction between the DLG5 and CARD15 genes and assessed possible association of DLG5 with clinical features of Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: DLG5 R30Q and the CARD15 polymorphisms, Arg702Trp, Gly908Arg and Leu1007fs were genotyped in 1,148 IBD cases and 749 controls. DLG5 R30Q was also analysed in cases stratified by CARD15 genotype, disease subtype and smoking history. RESULTS/FINDINGS: No significant difference in frequencies of the R30Q variant was observed between IBD cases (9.9%) and controls (10.1%) or in cases analysed separately as CD and UC. There was also no significant difference in the frequency of R30Q between CD cases carrying risk-associated CARD15 alleles and those that did not. The frequency of R30Q was higher in CD cases with ileal disease than cases without (p=0.042) and higher in CD cases who had smoked than in nonsmokers (p=0.009). INTERPRETATION/CONCLUSION: 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.