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  • Title: Clinical and genetic risk factors for perianal Crohn's disease in a population-based cohort.
    Author: Eglinton TW, Roberts R, Pearson J, Barclay M, Merriman TR, Frizelle FA, Gearry RB.
    Journal: Am J Gastroenterol; 2012 Apr; 107(4):589-96. PubMed ID: 22158027.
    Abstract:
    OBJECTIVES: Perianal Crohn's disease (CD) affects around one-quarter of CD patients and represents a distinct disease phenotype. The objective of this study was to investigate a large population-based cohort of inflammatory bowel disease (IBD) patients to identify clinical and genetic risk factors for perianal CD. METHODS: Data were collected in the Canterbury IBD database, estimated to include 91% of all patients with IBD in Canterbury, New Zealand. Genotyping was performed for selected loci previously demonstrated to be associated with CD. Patients with perianal disease were then compared with both CD patients without perianal disease and healthy controls to assess the presence of potential phenotypic, environmental, and genetic risk factors. RESULTS: Of the 715 CD patients in the database, 190 (26.5%) had perianal disease. In all, 507 patients with genotype data available were analyzed. Perianal disease was associated with younger age at diagnosis (P < 0.0001), complicated intestinal disease (P < 0.0001), and ileal disease location (P = 0.002). There was no association with gender, ethnicity, smoking, or breast feeding. Genotype analysis revealed an association with the neutrophil cytosolic factor 4 (NCF4) gene compared with both non-perianal CD patients (odds ratio (OR): 1.47; 95% confidence interval (CI): 1.08-1.99) and healthy controls (OR: 1.47; 95% CI: 1.10-1.95). There was no association identified with other genes, including IBD5 (OR: 0.91; 95% CI: 0.69-1.20), tumor necrosis factor α (OR: 1.04; 95% CI: 0.56-1.85), and IRGM (immunity-related guanosine triphosphatase protein type M) (OR: 1.21; 95% CI: 0.80-1.82). CONCLUSIONS: This study suggests that younger age at diagnosis, complicated disease behavior, and ileal disease location are risk factors for perianal CD. In addition, this paper represents the first report of an association of the NCF4 gene with perianal disease.
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