Document Detail


Mutation in TAGAP Is Protective of Anal Sepsis in Ileocolic Crohn's Disease.
MedLine Citation:
PMID:  23044675     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Tara M Connelly; Rishabh Sehgal; Arthur S Berg; John P Hegarty; Sue Deiling; David B Stewart; Lisa S Poritz; Walter A Koltun
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Diseases of the colon and rectum     Volume:  55     ISSN:  1530-0358     ISO Abbreviation:  Dis. Colon Rectum     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372764     Medline TA:  Dis Colon Rectum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1145-52     Citation Subset:  IM    
Affiliation:
Division of Colon and Rectal Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
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