Association of NOD2/CARD15, DLG5, OCTN1 and toll-like receptor 4 gene polymorphisms with inflammatory bowel disease: A university hospital experience

Background: Both genetic and environmental factors play major roles in the development of inflammatory bowel disease (IBD). Recent studies have identified a number of genetic susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). Objectives: The present study aimed at examining the association of nine polymorphisms in four different genes with the development of CD and UC in a sample of Saudi patients with IBD. Materials and Methods: All gene polymorphisms were identified by polymerase chain reaction and by direct sequencing. Allele and genotype frequencies of polymorphisms of NOD2/CARD15 (R702W, G908R, L1007finsC), Toll-like receptor 4 (TLR4) (D299G, T399I), OCTN promoter (C1672, G207C) and DLG5 (G113A, C4136A) genes were determined in Saudi subjects with CD (51), UC (26) and in 75 normal controls. Results: Out of the nine polymorphisms studied in four loci, only two polymorphisms in two different loci were found to have increased in patients compared with the control subjects. The CT genotype of TLR4 T3991 was over represented in patients with CD or UC compared to that in controls (odds ratios [OR], 5.63:95% confident interval [CI], 1.19-26.69; P = 0.03). In addition, the GA genotype of DLG5 G113A was over represented in patients with CD or UC compared with that in controls (OR, 4.72:95% CI 2.30-9.66; P = 0.0001). However, there were no significant associations found between all other polymorphisms studied and the susceptibility of CD or UC found in the Saudi population. Conclusion: Our finding indicates that association of IBD with nine gene polymorphisms was only significant in two of these polymorphic variants.