Faculty Collaboration Database

Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in men. Hum Genet 2006 Apr;119(3):305-11

Date

02/01/2006

Pubmed ID

16446977

DOI

10.1007/s00439-006-0133-1

Scopus ID

2-s2.0-33645012263 (requires institutional sign-in at Scopus site)   58 Citations

Abstract

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.

Author List

Friedrichs F, Brescianini S, Annese V, Latiano A, Berger K, Kugathasan S, Broeckel U, Nikolaus S, Daly MJ, Schreiber S, Rioux JD, Stoll M

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Crohn Disease
Female
Genetic Predisposition to Disease
Genetic Variation
Humans
Infant, Newborn
Inheritance Patterns
Male
Membrane Proteins
Middle Aged
Sex Characteristics
Tumor Suppressor Proteins