Association of DLG5 variants with inflammatory bowel disease in the New Zealand Caucasian population and meta-analysis of the DLG5 R30Q variant

Background: Variants in the DLG5 gene have been associated with inflaminatory bowel disease (IFID) in samples from some, but not all populations. In particular, 2 nonsynonymous single-nucleofide polymorphisms (SNPs), R30Q (rsl248696) and P1371Q (rs2289310), have been associated with an increased risk of IBD, and a common haplotype (called haplotype "A") has been associated with reduced risk. Methods: We genotyped R30Q, P1371Q, and a haplotype A tagging SNP (rs228931 1) in a New Zealand Caucasian cohort of 389 Crohn's disease (CD) patients, 406 ulcerative colitis (UC) patients, and 416 population controls. Each SNP was tested for association with disease susceptibility and clinical phenotypes. We also performed a meta-analysis of R30Q data from published association studies. Results: The haplotype A tagging SNP was associated with reduced risk of 1BD at the 0.05 significance level (P = 0.036) with an allefic odds ratio of 0.83 (95% confidence interval [CI]: 0.690.99). Association with haplotype A was strongest (odds ratio similar to 0.57) in UC patients with familial IBD or extraintestinal manifes-tations. The R30Q and P1371Q polymorphisins were not significantly associated with UC, CD, or IBD. Analysis of male and female data did not find any gender-specific associations. Meta-analysis gave no evidence of association of R30Q with 113D. Conclusions: Meta-analysis demonstrates that the minor allele of R30Q is not a risk factor for IBD across populations. 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.