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

Z Lin,T.Y Li,L Poritz,A Franke,S Schreiber,N.J Thomas,Y Wang,K.A Byrnes,R Wu,C Macneill,A.W Gebhard,A Ruether,W.A Koltun

doi:10.1155/2009/167534

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 femalep=0.015 vs 0.241 (IBD),p=0.024 vs 0.190 (CD), andp=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.

Highlights

Inflammatory bowel disease (IBD), consisting of two major subgroups Crohn’s disease (CD) and ulcerative colitis (UC), is a heterogeneous disease of intestinal inflammation, whose cause and clinical expression are affected by both genetic and environmental factors [1,2,3]
The statistical analysis showed that the R30Q variant was significantly associated with IBD (OR = 2.131, 95% CI 1.233–3.684, χ2 = 7.541, p = 0.006) (Table 2)
The results presented here support the previous finding that R30Q is a male-specific association in CD [27], and further reveals that the male-specific association of the R30Q variant is seen in UC, and in IBD overall in the studied populations

Summary

Introduction

Inflammatory bowel disease (IBD), consisting of two major subgroups Crohn’s disease (CD) and ulcerative colitis (UC), is a heterogeneous disease of intestinal inflammation, whose cause and clinical expression are affected by both genetic and environmental factors [1,2,3]. Evidence from both animal models and human studies, Z. Using genome-wide association technique, additional IBD associated genes/regions have been identified These include TNFSF15 [14], IL23R [15], ATG16L1 [16,17], the 5p13.1 region [18], and IRGM, NKX2-3 and PTPN2 [19,20]. This association of the R30Q variant with IBD was male-specific

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Conclusion