title: Perianal Crohn's disease: predictive factors and genotype-phenotype correlations.
abstract: OBJECTIVE
  To investigate genotype-phenotype correlations in patients with perianal Crohn's disease (PCD) in order to determine which factors predispose to development of perianal disease in Crohn's patients.
  
  
  METHODS
  Seven-hundred and ninety-five Caucasian individuals (317 CD patients and 478 controls without inflammatory bowel disease, IBD) were prospectively enrolled into a clinical/genetic database. Demographic and clinical data, as well as peripheral blood leukocyte DNA were obtained from all patients. The following were evaluated: three NOD2/CARD15 polymorphisms: R702W, G908R, and 1007insC; five IL-23r risk alleles: rs1004819, rs10489629, rs2201841, rs11465804, and rs11209026; a well-characterized single-nucleotide polymorphism (SNP) on the IBD5 risk haplotype (OCTN1) and two peripheral tag SNPs (IGR2060 and IGR3096).
  
  
  RESULTS
  PCD occurred in 147 (46%) of CD patients. There was no significant difference in the age at disease diagnosis between non-PCD and PCD patients (33 vs. 29 years, respectively). PCD patients were more likely to have disease located in the colon and ileocolic regions (79 PCD vs. 57% non-PCD; n = 116 vs. n = 96; p < 0.001), whereas patients with non-PCD were more likely to have Crohn's within the terminal ileum and upper gastrointestinal tract (43% non-PCD vs. 21% PCD; n = 73 vs. n = 31; p < 0.05). Thirty-four percent of patients with PCD required a permanent ileostomy (n = 50) compared to only 4% of non-PCD patients (n = 6; p < 0.05). Mutations in CARD15/NOD2 and IL-23r were risk factors for CD overall; however, in contrast to prior reports, in this patient population, OCTN1 and IGR variations within the IBD5 haplotype were not significant predictors of PCD.
  
  
  CONCLUSIONS
  Colon/ileocolic CD location appears to be a significant predictor of perianal manifestations of CD. Patients with PCD are more likely to require permanent fecal diversion. We did not identify any genetic variations or combination of clinical findings and genetic variations within the CARD15/NOD2, IL-23r, and OCTN1 genes or IGR that were predictive of PCD.
authors.affiliation: The Price Institute of Surgical Research and the Section of Colon and Rectal Surgery, Department of Surgery, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Kanaan
authors.forename: Surriya
authors.initials: S
authors.lastname: Ahmad
authors.forename: Natalia
authors.initials: N
authors.lastname: Bilchuk
authors.forename: Crystal
authors.initials: C
authors.lastname: Vahrenhold
authors.forename: Jianmin
authors.initials: J
authors.lastname: Pan
authors.forename: Susan
authors.initials: S
authors.lastname: Galandiuk
mesh_terms: D000328:Adult; D017677:Age Distribution; D000483:Alleles; D001003:Anal Canal; D016022:Case-Control Studies; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012002:Rectal Diseases / Q000453:epidemiology / Q000235:genetics*; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D027981:Symporters; D055815:Young Adult
chemical_list: D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters