GENETIC-MARKERS MAY PREDICT DISEASE BEHAVIOR IN PATIENTS WITH ULCERATIVE-COLITIS

Background & Aims: Recent studies have suggested that HLA DRB10103 an d allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene pred ict 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 performe d in 99 patients and 472 controls. Genotyping for polymorphisms of gen es encoding tumor necrosis factor alpha and IL-1RA was performed in 10 7 patients and 89 controls, Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects b y fixed neutrophil enzyme-linked immunosorbent assay and indirect immu nofluorescence. Results: The DRB10103 allele was increased in patient s (14.1% vs. 3.2% in controls; P < 1 x 10(-5)). This association was g reatest in patients with extensive disease (15.8%; P < 0.0001) or extr aintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0 001). The DRB104 alleles were reduced in patients (P = 0.005), Differ ences 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 in creased in ANCA-positive patients. Conclusions: Genetic markers may pr edict disease behavior in ulcerative colitis.