Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

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.