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Crohn’s disease–related single nucleotide polymorphisms are associated with ileal pouch afferent limb stenosis

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

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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Funding

This work was supported by the John W. Price and Barbara Thruston Atwood Price Trust and a grant from the Mary K. Oxley Foundation.

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Authors and Affiliations

  1. Price 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

    Stephen J. O’Brien, Jacob Hallion, Katharina M. Scheurlen, Casey Fiechter, James Burton, Mason Paas, Miranda Schmidt, Sarah Gardner, Maurice R. Eichenberger & Susan Galandiuk

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

    Jianmin Pan & Shesh Rai

Authors
  1. Stephen J. O’Brien
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  2. Jacob Hallion
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  3. Katharina M. Scheurlen
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  4. Casey Fiechter
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  12. Susan Galandiuk
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Contributions

Study concept: SG, SOB, ME. Data acquisition: SOB, JH, KS, CF, JB, MP, MS, SG, ME. Statistical analysis: SOB, KS, JP, SR. Drafting of the manuscript: SOB, JH, KS, CF, ME. Critical review of the manuscript: SOB, JH, KS, CF, JB, MP, MS, SG, ME, JP, SR, SG. Approval of the final draft: SOB, JH, KS, CF, JB, MP, MS, SG, ME, JP, SR, SG.

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Correspondence to Susan Galandiuk.

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O’Brien, S.J., Hallion, J., Scheurlen, K.M. et al. Crohn’s disease–related single nucleotide polymorphisms are associated with ileal pouch afferent limb stenosis. J Gastrointest Surg 25, 2377–2386 (2021). https://doi.org/10.1007/s11605-020-04884-0

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  • DOI: https://doi.org/10.1007/s11605-020-04884-0

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