Authors:
E. A. M. Festen, A. Zhernakova, L. Franke, G. Trynka, C. C. van Diemen, M. Bevova, R. M. Nijmeijer, R. Heijmans, H. M. Boezen, D. A. Van Heel, A. A. van Bodegraven, P. C. F. Stokkers, C. Wijmenga, B. A. Crusius,and R. K. Weersma
Summary:
The two main phenotypes of inflammatory bowel disease (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC) - are chronic intestinal inflammatory disorders with a complex genetic background.
We performed a functional candidate gene analysis within the innate immune pathway in IBD using a three-stage design. In phase I, 354 SNPs from 85 innate immunity genes were typed in a cohort of 520 Dutch IBD patients (284 CD, 236 UC) and 808 controls. In phase II, 9 SNPs showing association at p<0.006 in phase I were replicated in a second independent cohort of 545 Dutch IBD patients (326 CD, 219 UC) and 360 controls. In phase III, 3 SNPs with p<0.01 in the combined phase I and phase II analysis were genotyped in an additional cohort of 786 Dutch IBD samples (452 CD, 334 UC) and 768 independent controls. Joint analysis of 1,851 IBD patients (1062 CD, 789 UC) and 1936 controls demonstrated strong association to the IL18RAP gene for both CD and UC (p IBD 1.9E-8, OR 1.35). Association in CD is independently supported by the Crohn's disease dataset of the Wellcome Trust Case Control Consortium. In addition, an association of the CARD9 variant to CD and UC was observed (pIBD=3.25E-5, OR 1.21). Both genes are located in extended haplotype blocks on 2q11-2q12 and 9q34.3, respectively. Our results indicate two novel IBD loci and further support the importance of the innate immune system in the predisposition to both CD and UC.
Source:
11th Annual Meeting of the American Society of Gene Therapy; 05/28/08 - 06/01/08