Search in the Abstract Database

Search Abstracts 2013

* = Presenting author

P675. A locus on chromosome 8q24 near MYC and anti-OmpC are associated with perianal Crohn's disease

T.B. Murdoch1, A.V. Weizman2, W. Xu3, A.M. Griffiths4, T.D. Walters4, A.H. Steinhart2, R. Milgrom2, J.M. Stempak2, M.S. Silverberg2, 1University of Calgary, Division of Gastroenterology, Calgary, Canada, 2Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases, Toronto, Canada, 3University of Toronto, Dalla Lana School of Public Health, Toronto, Canada, 4Hospital for Sick Children, Division of Gastroenterology, Toronto, Canada

Background

Genetic studies have provided key insights into Crohn's disease pathogenesis. However, the genetic and clinical factors underlying specific Crohn's disease phenotypes, such as perianal disease, are poorly understood. In the present study, we aimed to elucidate the genetic, clinical, and serologic predictors of perianal disease.

Methods

Caucasian patients with Crohn's disease from Mount Sinai Hospital and Hospital for Sick Children, Toronto were included (n = 849). Charts were reviewed for clinical parameters. We performed a genome-wide association study (GWAS) using Illumina OmniExpress, comparing patients with and without perianal disease (n = 780). Serum was analyzed by ELISA for anti-Saccharomyces cerevisiae (ASCA), anti-outer membrane porin C (anti-OmpC), anti-Cbir1, and anti-Pseudomonas fluorescens (anti-I2). Data analysis was undertaken using univariate logistic regression for clinical and serologic data (statistical significance at p < 0.001). Multivariate regression was used for GWAS data, with principal components/disease location as covariates. We report single nucleotide polymorphisms (SNPs) that reached p = 10E-6.

Results

Perianal disease was documented in 35% (n = 297). Perianal disease was associated with colonic and ileocolonic disease locations (p < 0.0001), as well as with upper GI (p = 0.0006) and rectal disease (p < 0.0001). Anti-OmpC was significantly more prevalent among individuals with perianal disease (p < 0.0001). Two statistically significant SNPs were identified. One was a SNP at chromosome 8q24 (rs6470545, p = 9×10−6), which is 200 kilobases upstream from the proto-oncogene MYC, and near a colon cancer locus (rs6983267) known to control MYC expression. Three nearby SNPs (rs10091329, rs6470537, rs6470552) in close linkage disequilibrium (r2 > 0.8) had p-values of 10E-5. Another SNP on chromosome 8 in a gene desert was also associated with perianal disease (rs10092418, p = 8×10−6).

Conclusion

We report novel genetic and serologic associations with perianal disease in a large cohort of Crohn's disease patients. The association between perianal disease and a locus near MYC, which encodes a transcription factor with broad activity in cell proliferation, apoptosis, and differentiation, suggests novel mechanisms in the development of perianal disease. Replication will be important to confirm findings and direct further investigation into this unique Crohn's disease phenotype.

*Dr. Murdoch and Dr. Weizman contributed equally to this study.