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.
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; Richard Kirsch; Raquel Milgrom; Joanne M Stempak; Boyko Kabakchiev; Mark S Silverberg Journal: Inflamm Bowel Dis Date: 2016-04 Impact factor: 5.325
Authors: Gian Eugenio Tontini; Maurizio Vecchi; Luca Pastorelli; Markus F Neurath; Helmut Neumann Journal: World J Gastroenterol Date: 2015-01-07 Impact factor: 5.742
Authors: Leandro Minatel Vidal de Negreiros; Lívia Bitencourt Pascoal; Lívia Moreira Genaro; Julian Furtado Silva; Bruno Lima Rodrigues; Michel Gardere Camargo; Carlos Augusto Real Martinez; Cláudio Saddy Rodrigues Coy; Maria de Lourdes Setsuko Ayrizono; João José Fagundes; Raquel Franco Leal Journal: Am J Transl Res Date: 2022-07-15 Impact factor: 3.940
Authors: Kathleen M Schieffer; Justin R Wright; Leonard R Harris; Sue Deiling; Zhaohai Yang; Regina Lamendella; Gregory S Yochum; Walter A Koltun Journal: J Crohns Colitis Date: 2017-10-27 Impact factor: 9.071