A Single Nucleotide Polymorphism in the STAT5 Gene Favors Colonic as Opposed to Small-Bowel Inflammation in Crohn’s Disease

• Published in: Diseases of the colon & rectum Vol. 56; no. 9; pp. 1068 - 1074
• Main Authors: Connelly, Tara M., Koltun, Walter A., Berg, Arthur S., Hegarty, John P., Brinton, David, Deiling, Sue, Poritz, Lisa S., Stewart, David B.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MDc The American Society of Colon and Rectal Surgeons 01.09.2013; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Biological and medical sciences; Cohort Studies; Colitis - genetics; Crohn Disease - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Markers; Genotype; Genotyping Techniques; Humans; Ileitis - genetics; Logistic Models; Male; Medical sciences; Other diseases. Semiology; Polymorphism, Single Nucleotide; Retrospective Studies; STAT5 Transcription Factor - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Young Adult; Inflammation; Crohn's disease; Small intestine; Inflammatory disease; Crohn disease; Phenotype; SNP; Gastroenterology; Digestive diseases; Genetics; Intestinal disease; STAT5; Colon; Single nucleotide polymorphism; Polymorphism
• ISSN: 0012-3706; 1530-0358; 1530-0358
• DOI: 10.1097/DCR.0b013e31829de128

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.