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Disease Markers
Volume 27, Issue 5, Pages 193-201
http://dx.doi.org/10.3233/DMA-2009-0662

Genetic Association of DLG5 R30Q with Familial and Sporadic Inflammatory Bowel Disease in Men

Z. Lin,1 L. Poritz,1 A. Franke,2 T.Y. Li,3 A. Ruether,2 K.A. Byrnes,1 Y. Wang,4 A.W. Gebhard,1 C. MacNeill,5 N.J. Thomas,6 R. Wu,7 S. Schreiber,2,8 and W.A. Koltun1

1Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
2Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
3Total Health Management and Technology, Inc., Philadelphia, Pennsylvania, USA
4Department of Molecular and Cellular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
5Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
6Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
7Center for Statistical Genetics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
8Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany

Received 18 December 2009; Accepted 18 December 2009

Copyright © 2009 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania.

Methods: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex™ Genotyping System in 473 samples.

Results: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p=0.006), and separately with CD (p=0.009) and UC (p=0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs female p=0.015 vs 0.241 (IBD), p=0.024 vs 0.190 (CD), and p=0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p=0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families.

Conclusions: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific.