Diseases of the Colon & Rectum

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Diseases of the Colon & Rectum:
doi: 10.1097/DCR.0b013e3182676931
Original Contributions: Inflammatory Bowel Disease

Mutation in TAGAP Is Protective of Anal Sepsis in Ileocolic Crohn’s Disease

Connelly, Tara M. M.B., B.Ch.; Sehgal, Rishabh M.B., B.Ch., M.R.C.S.; Berg, Arthur S. Ph.D.; Hegarty, John P. Ph.D.; Deiling, Sue B.A.; Stewart, David B. M.D.; Poritz, Lisa S. M.D.; Koltun, Walter A. M.D.

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BACKGROUND: Anal complications of Crohn’s disease range from painless skin tags to debilitating fistulas that are imperfectly treated with tumor necrosis factor antagonists. The recent discovery of more than 190 single-nucleotide polymorphisms associated with Crohn’s disease offers the opportunity to genetically define the severity of anal disease in Crohn’s disease and possibly predict prognosis and anti-tumor necrosis factorresponse.

OBJECTIVES: This study aimed to identify single nucleotide polymorphisms associated with anal disease generally, septic anal disease specifically and the responsivity to anti-tumor necrosis factor treatment.

DESIGN: All patients with ileocolonic Crohn’s disease were identified from our IBD registry. One hundred ninety-six Crohn’s disease-related single-nucleotide polymorphisms were analyzed by the use of a custom microarray chip. Patients’ response to anti-tumor necrosis factor treatment was then assessed.

RESULTS: One hundred sixteen patients with ileocolonic Crohn’s disease were identified and assigned to septic anal disease (abscesses/fistulas, n = 35), benign anal disease (skin tags/fissures/isolated pain, n = 17), and no anal disease (n = 64) cohorts. Single-nucleotide polymorphism rs212388 negatively correlated with the presence of anal disease overall and septic disease specifically. The presence of the non-wild-type allele G was protective of anal sepsis with homo- and heterozygotes having a 75% chance of no anal disease (p = 0.0001). The homozygous wild-type group had the highest risk of septic disease and included 3 of 4 patients requiring diverting ileostomies. Twenty-four patients were treated with anti-tumor necrosis factors. Nine had a beneficial response (assessed at >6 months); however, no single-nucleotide polymorphism correlated with anti-tumor necrosis factor response. Rs212388 is associated with the TAGAP molecule involved in T-cell activation.

CONCLUSIONS: Rs212388 most significantly correlated with the presence and severity of anal disease in ileocolonic Crohn’s disease. A single copy of the risk allele was protective, whereas wild-type homozygotes had the highest risk of septic disease and stoma creation. In this select group, no single-nucleotide polymorphism was predictive of anti-tumor necrosis factor response. Mutations in TAGAP may predict a more benign form and course of anal disease in Crohn’s disease.

© The ASCRS 2012


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