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Background: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. Methods: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. Results: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. Conclusion: DLG5 30Q is associated with a small reduction in risk of CD in women.Inflammatory bowel disease (IBD; OMIM 266600) comprises Crohn disease (CD; OMIM 266600) and ulcerative colitis (UC; OMIM 191390). Epidemiological and genetic studies have demonstrated that genes play an important role in the pathogenesis of IBD.1-6 Genetic variants associated with CD have been identified and replicated in the CARD15/NOD2 gene (OMIM 605956) 7-9 and in the chromosome 5q31 region (OMIM 606348), 10-13 and recently, the first generation of whole-genome association studies have identified multiple new susceptibility variants. [14][15][16][17][18][19] In 2004, Stoll et al described an association between IBD and DLG5 variants (DLG5: Drosophila Discs Large Homolog 5 (OMIM 604090). In particular, p.R30Q (c.89GRA, rs1248696, previously reported as c.113GRA) was found to be associated with IBD in a German family cohort. Stoll et al 20 replicated the R30Q association with CD in a European case-control cohort and found a non-significant overtransmission of the 30Q allele in patients with CD in a German/UK family cohort. Subsequently, Daly et al 21 replicated the association of 30Q with CD in one of two case-control cohorts and in a family cohort. However, subsequent studies have failed to replicate the association of DLG5 30Q with CD. 22-34Recently, Friedrichs et al 35 examined genderstratified data from the case-control cohorts showing association in the initial two DLG5 studies, 20 21 and found that the DLG5 30Q allele ...

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