Abstract

Crohn's disease-related single nucleotide polymorphisms are associated with ileal pouch afferent limb stenosis

J Gastrointest Surg. 2021 Sep;25(9):2377-2386. doi: 10.1007/s11605-020-04884-0.Epub 2021 Jan 14.

Stephen J O'Brien 1, Jacob Hallion 1, Katharina M Scheurlen 1, Casey Fiechter 1, James Burton 1, Mason Paas 1, Miranda Schmidt 1, Sarah Gardner 1, Maurice R Eichenberger 1, Jianmin Pan 2, Shesh Rai 2, Susan Galandiuk 3

 
     

Author information

1Price Institute of Surgical Research, The Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, 550 South Jackson Street, Louisville, KY, 40202, USA.

2Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA.

3Price Institute of Surgical Research, The Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, 550 South Jackson Street, Louisville, KY, 40202, USA. susan.galandiuk@louisville.edu.

Abstract

Background: Ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis. Afferent limb stenosis is an infrequent complication following IPAA, suggesting underlying Crohn's disease (CD). We hypothesized that CD-related single nucleotide polymorphisms (SNPs) are associated with afferent limb stenosis.

Methods: Afferent limb stenosis and CD control group patients were recruited from a prospective institutional inflammatory bowel disease database and associated biobank. Patient demographics, Montreal classification, and medication use were recorded. Ten SNPs associated with stricturing Crohn's disease were examined in genomic DNA and compared among afferent limb stenosis, stricturing CD, and non-stricturing CD controls.

Results: Twenty-seven afferent limb stenosis and 162 CD control group patients (108 stricturing, 54 non-stricturing) were identified. Patients were gender and race matched. Afferent limb stenosis and stricturing CD controls were younger at diagnosis (Montreal A1/A2 vs. A3) compared to non-stricturing CD controls (both p < 0.05). The majority of afferent limb stenosis patients were non-smokers compared to CD controls (74% vs. 36%, p < 0.01) and did not use biologic therapies (4% vs. 37%, p < 0.001). The FUT2 G allele was more frequent in afferent limb stenosis and stricturing CD controls compared to non-stricturing CD controls (both p < 0.05). The NOD2 T allele was more frequent in stricturing CD controls compared to afferent limb stenosis and non-stricturing CD controls (both p < 0.05).

Conclusion: Afferent limb stenosis patients are phenotypically similar to stricturing CD controls, but differ with lower smoking rates and lower NOD2 allele frequency. Such differences could contribute to the presentation delay with a stricturing phenotype. Selective SNP assessment may help categorize patients likely to develop afferent limb stenosis.

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