Background: Crohn's disease is a chronic inflammatory ailment that can affect the colon and/or small intestine. A genetic basis for disease distribution is being sought, although the available data are seminal. The STAT5 gene is known to influence colonic permeability, mucosal regeneration, and interleukin 2 production, although its role in the distribution of Crohn's disease is unclear. Objective: The aim of this study was identification of single nucleotide polymorphisms associated with Crohn's distribution, with the goal of distinguishing disease subcategories and differing pathophysiologies. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted in a single tertiary referral center. Patients: A total of 173 patients with Crohn's disease who were identified from our biobank were segregated by disease distribution (colitis, n = 28; ileocolic disease, n = 116; enteritis, n = 29) and were genotyped for 258 Crohn's-associated single nucleotide polymorphisms. Patients with ulcerative colitis (n = 119) were also genotyped to confirm the association of identified single nucleotide polymorphisms with small-bowel sparing, colonic pathology. Main Outcome Measures: We investigated an association between single nucleotide polymorphisms and Crohn's disease distribution. Results: Single nucleotide polymorphism rs16967637 in the STAT5 gene was associated with small-bowel sparing Crohn's disease when the enteritis group was compared with either a combined colitis/ileocolic group (p = 0.025) or those with only ileocolic disease (p = 0.04). Homozygosity for the at-risk allele (C) was present in 59% of patients with sparing of the small bowel. The association of this single nucleotide polymorphism with small-bowel sparing disease persisted when patients with ulcerative colitis were compared with the group with Crohn's enteritis (p = 0.036), as well as after combining patients with ulcerative colitis with both the Crohn's colitis group (p = 0.009) and the Crohn's ileocolitis/colitis group (p = 0.00008). Limitations: This study was limited by the small numbers of study subjects with isolated enteritis or colitis. Conclusions: Single nucleotide polymorphism rs16967637 in the STAT5 gene was the only single nucleotide polymorphism associated with Crohn's disease without enteritis. Homozygosity for the atrisk allele demonstrated the strongest association with this phenotype. These results suggest a role for this single nucleotide polymorphism in the development of inflammatory bowel disease of the large intestine.
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