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Am J Gastroenterol. 2007 Feb;102(2):391-8. Epub 2006 Dec 11.

DLG5 R30Q variant is a female-specific protective factor in pediatric onset Crohn's disease.

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1
Department of Pediatrics, Medical College Wisconsin, Milwaukee, Wisconsin 53226, USA.

Abstract

OBJECTIVE:

A significant association between the DLG5 variant (R30Q) and inflammatory bowel disease (IBD) has been confirmed in several independent adult IBD cohorts. There is growing evidence that gender significantly influences R30Q susceptibility in Crohn's disease (CD). Pediatric onset CD features a significantly lower incidence for female children compared with male children. We, therefore, studied the influence of gender on R30Q susceptibility in an exclusively pediatric onset IBD cohort.

DESIGN:

A total of 281 CD (181 trios) and 479 population-based controls were genotyped for DLG5 R30Q using Taqman assay. Association was tested by case-control and transmission disequilibrium testing analysis. Multivariate logistic regression was performed to investigate gene-gene and gene-gender interactions, as well as genotype-phenotype correlations.

RESULTS:

Overall allele frequency for R30Q was 8.5% in CD and 10.3% in controls. Logistic regression showed R30Q had no association with CD (OR 0.81, 95% CI 0.55-1.20, P= 0.3) when the cohort was analyzed as a whole. Stratified by gender, a significant negative association was detected for R30Q in female children (OR 0.39, 95% CI 0.2-0.77, P= 0.006), but not in male children. Gender was found to be an effect modifier of the association between R30Q and CD as the odds ratios in female children and male children differed significantly. The gender-specific association of R30Q and CD was independent of additional CD risk factors such as CARD15 and IBD5.

CONCLUSIONS:

DLG5 has a gender-specific role in the susceptibility of pediatric CD. Specifically, the significant negative association found between DLG5 R30Q and CD in female children suggests DLG5 may have a protective effect in CD susceptibility for female children.

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