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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 at-risk 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.

(C) 2013 The American Society of Colon and Rectal Surgeons