title: Perianal Crohn's Disease is Associated with Distal Colonic Disease, Stricturing Disease Behavior, IBD-Associated Serologies and Genetic Variation in the JAK-STAT Pathway.
abstract: BACKGROUND
  Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD.
  
  
  METHODS
  We performed a case-control study comparing patients with (pCD+) and without perianal (pCD) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms.
  
  
  RESULTS
  We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P = 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P = 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P = 5.11 × 10), TNF alpha pathways (NUCB2, P = 8.68 × 10; DAPK1), IFNg pathways (DAPK1; NDFIP2, P = 8.74 × 10), and extracellular matrix and scaffolding proteins (USH1C, P = 8.68 × 10; NDFIP2; TMC07, P = 8.87 × 10). Pathway analyses implicated the JAK-Stat pathway (pc = 3.72 × 10).
  
  
  CONCLUSIONS
  We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.
authors.affiliation: *F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; †Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; ‡Division of Hematology and Oncology, Department of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California; and §Pediatric Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Manreet
authors.initials: M
authors.lastname: Kaur
authors.forename: Deepa
authors.initials: D
authors.lastname: Panikkath
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yan
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Liu
authors.forename: Dror
authors.initials: D
authors.lastname: Berel
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.forename: Eric A
authors.initials: EA
authors.lastname: Vasiliauskas
authors.forename: Andrew
authors.initials: A
authors.lastname: Ippoliti
authors.forename: Marla
authors.initials: M
authors.lastname: Dubinsky
authors.forename: David Q
authors.initials: DQ
authors.lastname: Shih
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Phillip
authors.initials: P
authors.lastname: Fleshner
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001004:Anus Diseases / Q000150:complications*; D016022:Case-Control Studies; D003108:Colonic Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003251:Constriction, Pathologic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D053612:Janus Kinases / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000235:genetics*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053612:Janus Kinases