Genetic association of DLG5 R30Q with familial and sporadic inflammatory bowel disease in men

Article type: Research Article

Authors: Lin, Z. | Poritz, L. | Franke, A. | Li, T.Y. | Ruether, A. | Byrnes, K.A. | Wang, Y. | Gebhard, A.W. | MacNeill, C. | Thomas, N.J. | R. Wu, | Schreiber, S.^; | Koltun, W.A.

Affiliations: Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA | Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany | Total Health Management and Technology, Inc., Philadelphia, Pennsylvania, USA | Department of Molecular and Cellular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA | Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA | Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA | Center for Statistical Genetics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA | Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany

Note: [] Corresponding authors: Walter A. Koltun MD, Department of Surgery, The Pennsylvania State University College of Medicine, 500 University Drive, H 137, Hershey, Pennsylvania 17033. Tel.: +717 531 5164; Fax: +717 531 0646; E-mail: [email protected]; Zhenwu Lin PhD, Department of Surgery, The Pennsylvania State University College of Medicine, 500 University Drive, H 137, Hershey, Pennsylvania 17033. Tel.: +717 531 6196; Fax: +717 531 0646; E-mail: [email protected]

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.

Keywords: DLG5 R30Q, familial IBD registry, genetic association, inflammatory bowel disease, male-specific

DOI: 10.3233/DMA-2009-0662

Journal: Disease Markers, vol. 27, no. 5, pp. 193-201, 2009