Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in men.
Recently, we described the association of genetic variation in the discs large homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) in a large European study sample (Stoll et al. in Nat Genet 36:476-480, 2004). Here, we report that the R30Q variant constitutes a susceptibility factor for Crohn disease (CD) in men [odds ratio (OR)=2.49, 95% confidence interval (CI) 1.53-4.06, P<0.001] but not women (OR=1.01, 95% CI=0.70-1.45, P=0.979) using multivariate logistic regression analyses in a unified study sample from Germany, Italy and Quebec. R30Q is a significant predictor for CD in men even when accounting for CARD15 and IBD5 risk variants (adjusted OR=2.41, 95% CI=1.41-4.12, P=0.001). The observed association is driven by a gender-dependent transmission ratio distortion (TRD) among healthy controls (frequency of Q allele: men 5.2%, women 11.3%), an effect that is offset in CD patients (frequency of Q allele: men 10.1%, women 10.9%). This finding is further substantiated by two non-IBD study samples, one of which consists of a newborn screening sample (newborn males 7.1%; newborn females 11%, P=0.036). Further investigation of the observed TRD may contribute towards enlightening the role of DLG5 in physiological processes influencing transmission of chromosomes to the surviving offspring, which, in turn, may help in understanding its implication in the development of CD among men.
Friedrichs
Frauke
F
Leibniz-Institute for Arteriosclerosis Research, Domagkstr. 3, 48149, Muenster, Germany.
Brescianini
Sonia
S
Annese
Vito
V
Latiano
Anna
A
Berger
Klaus
K
Kugathasan
Subra
S
Broeckel
Ulrich
U
Nikolaus
Susanna
S
Daly
Mark J
MJ
Schreiber
Stefan
S
Rioux
John D
JD
Stoll
Monika
M
D000328:Adult; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D040582:Inheritance Patterns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D012727:Sex Characteristics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C114461:DLG5 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins