title: Genetic markers may predict disease behavior in patients with ulcerative colitis.
abstract: OBJECTIVE
  Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis.
  
  
  METHODS
  HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence.
  
  
  RESULTS
  The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients.
  
  
  CONCLUSIONS
  Genetic markers may predict disease behavior in ulcerative colitis.
authors.affiliation: Nuffield Department of Medicine, Radcliffe Hospitals, Oxford, England.
authors.forename: M
authors.initials: M
authors.lastname: Roussomoustakaki
authors.forename: J
authors.initials: J
authors.lastname: Satsangi
authors.forename: K
authors.initials: K
authors.lastname: Welsh
authors.forename: E
authors.initials: E
authors.lastname: Louis
authors.forename: G
authors.initials: G
authors.lastname: Fanning
authors.forename: S
authors.initials: S
authors.lastname: Targan
authors.forename: C
authors.initials: C
authors.lastname: Landers
authors.forename: D P
authors.initials: DP
authors.lastname: Jewell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism*; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D005819:Genetic Markers