The NOD2insC polymorphism is associated with worse outcome following ileal pouch-anal anastomosis for ulcerative colitis.

Abstract

BACKGROUND:

Inflammatory complications after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) are common.

OBJECTIVE:

To investigate whether genetic factors are associated with adverse pouch outcomes such as chronic pouchitis (CP) and a Crohn's disease-like (CDL) phenotype.

DESIGN:

866 patients were recruited from three centres in North America: Mount Sinai Hospital (Toronto, Ontario, Canada), the Cleveland Clinic (Cleveland, Ohio, USA) and Penn State Milton S Hershey Medical Center (Hershey, Pennsylvania, USA). DNA and clinical and demographic information were collected. Subjects were classified into post-surgical outcome groups: no chronic pouchitis (NCP), CP and CDL phenotype.

RESULTS:

Clinical and genetic data were available on 714 individuals. 487 (68.2%) were classified as NCP, 118 (16.5%) CP and 109 (15.3%) CDL. The presence of arthritis or arthropathy (p=0.02), primary sclerosing cholangitis (p=0.009) and duration of time from ileostomy closure to recruitment (p=0.001) were significantly associated with outcome. The NOD2insC (rs2066847) risk variant was the single nucleotide polymorphism (SNP) most significantly associated with pouch outcome (p=7.4×10(-5)). Specifically, it was associated with both CP and CDL in comparison with NCP (OR=3.2 and 4.3, respectively). Additionally, SNPs in NOX3 (rs6557421, rs12661812), DAGLB (rs836518) and NCF4 (rs8137602) were shown to be associated with pouch outcome with slightly weaker effects. A multivariable risk model combining previously identified clinical (smoking status, family history of inflammatory bowel disease), serological (anti-Saccharomyces cerevisiae antibody IgG, perinuclear antineutrophil cytoplasmic antibody and anti-CBir1) and genetic markers was constructed and resulted in an OR of 2.72 (p=8.89×10(-7)) for NCP versus CP/CDL and 3.22 (p=4.11×10(-8)) for NCP versus CDL, respectively.

CONCLUSION:

Genetic polymorphisms, in particular, the NOD2insC risk allele, are associated with chronic inflammatory pouch outcomes among patients with UC and IPAA.

• Authors: Andrea D Tyler, Raquel Milgrom, Joanne M Stempak, Wei Xu, John Hunter Brumell, Aleixo M Muise, Rishabh Sehgal, Zane Cohen, Walter Koltun, Bo Shen, Mark S Silverberg
• Journal: Gut (Gut) Vol. 62 Issue 10 Pg. 1433-9 (Oct 2013) ISSN: 1468-3288 [Electronic] England
• PMID: 22879519 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• NOD2 protein, human
• Nod2 Signaling Adaptor Protein

Topics

• Acute Disease
• Adolescent
• Adult
• Child
• Child, Preschool
• Chronic Disease
• Colitis, Ulcerative (genetics, surgery)
• Colonic Pouches (adverse effects)
• Crohn Disease (etiology, genetics)
• Female
• Genetic Predisposition to Disease
• Humans
• Male
• Middle Aged
• Nod2 Signaling Adaptor Protein (genetics)
• Polymorphism, Single Nucleotide
• Pouchitis (etiology, genetics)
• Prognosis
• Retrospective Studies
• Risk Factors
• Treatment Outcome