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P653. Genetic predictors of non reversible tissue damage in inflammatory bowel disease

J.M. Benitez1, J.M. Mahachie John2, E. Théâtre3, C. Reenaers3, M. De Vos4, O. Dewit5, K. Van Steen2, E. Louis3, 1Reina Sofia University Hospital, IMIBIC, CHU Liège, Gastroenterology, Córdoba, Spain, 2CHU de Liège, Bioinformatics and Modeling, Liège, Belgium, 3CHU de Liège, GIGA, Gastroenterology, Liège, Belgium, 4Ghent University Hospital, Gastroenterology, Ghent, Belgium, 5Saint-Luc Hospital, Gastroenterology, Brussels, Belgium

Background

Genome-wide association studies and meta-analyses have identified more than 140 loci associated with inflammatory bowel disease (IBD), but so far the impact of these genetic regions on disease subphenotypes is unknown. We defined severe subphenotypes as forms of IBD which lead to the development of significant non reversible tissue damage such as a colectomy for ulcerative colitis (UC) and any colectomy, or at least two small bowel resections or a unique resection >50 cm or complex perianal fistulizing disease for Crohn's disease (CD).

We aimed to identify single nucleotide polymorphisms (SNPs) that were associated with the time to development of these bad outcomes in IBD.

Methods

We reviewed the data from 451 and 593 immunochiped UC and CD patients, respectively, from Liège, St-Luc Brussels and Ghent university hospital. We matched the UC and CD phenotype data with genetic data from the IIBDGC database. All the SNPs genotyped with the immunochips (156499 SNPs) were studied according to their impact on the time to development of any one of the bad outcomes previously defined. The analysis was carried out by Golden Helix Software (SVS).

Results

We analyzed combined UC and CD data including 1044 patients with a median of follow-up of 11.3 yrs. Out of 451 immunochiped UC patients, 20.6% needed colectomy (after a median time of 6.3 yrs). Out of 593 immunochiped CD patients, 40.3% had at least one of the considered bad outcomes after a median time of 6.1 yrs. After matching genotype and phenotype data, and doing quality controls 889 patients and 101051 SNPs were evaluable. Out of 101051 SNPs, 5349 SNPs were associated with the time to bad outcome at 5% level of significance, but when multiple testing corrections were performed none of the SNPs survived significance. When analysing CD and UC patients separately, 5601 and 4718 SNPs reached the uncorrected 5% level of significance, respectively. Statistical significance was lost after adjusting for multiple testing.

Conclusion

No individual Immunochip SNP was strongly associated with the time to non reversible tissue damage development in IBD as a whole. Further studies on larger cohort of patients are required to assess genetic associations with more homogenous severe subphenotypes in CD and UC separately.