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 inflammatory bowel disease (IBD) in samples from some, but not all populations. In particular, 2 nonsynonymous single-nucleotide polymorphisms (SNPs), R30Q (rs1248696) 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 (rs2289311) 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 IBD at the 0.05 significance level (P=0.036) with an allelic odds ratio of 0.83 (95% confidence interval [CI]: 0.69-0.99). Association with haplotype A was strongest (odds ratio approximately 0.57) in UC patients with familial IBD or extraintestinal manifestations. The R30Q and P1371Q polymorphisms 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 IBD.


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.
Browning
Brian L
BL
Discipline of Nutrition, Department of Statistics, University of Auckland, New Zealand, and Department of Gastroenterology, Box Hill Hospital, Monash, Australia. b.browning@auckland.ac.nz
Huebner
Claudia
C
Petermann
Ivonne
I
Demmers
Pieter
P
McCulloch
Alan
A
Gearry
Richard B
RB
Barclay
Murray L
ML
Shelling
Andrew N
AN
Ferguson
Lynnette R
LR
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009520:New Zealand; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People
C114461:DLG5 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins