title: Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL.
abstract: OBJECTIVE
  IKBL gene lies telomeric of the tumor necrosis factor cluster in the central major histocompatibility complex and carries a structural polymorphism at position +738. In the Spanish white population, we found the IKBL+738(C) allele in haplotypes carrying either HLA-DRB1(*)1501 or -DRB1(*)0103. Because these HLA class II alleles may confer susceptibility to ulcerative colitis, we investigated an association between IKBL+738(C) and this disease.
  
  
  METHODS
  DNA-based techniques were used to type individual alleles of HLA-DRB1 and IKBL+738. The frequencies of these alleles were compared among ethnically matched populations comprising 155 patients and 298 controls.
  
  
  RESULTS
  IKBL+738(C) allele was exclusively increased in patients with extensive and/or intractable disease. HLA-DRB1(*)0103 was the only HLA-DRB1 allele to be significantly increased in frequency in patients with UC compared with controls. It was found in patients with extensive and distal disease. In the HLA-DRB1(*)0103-negative population, patients with extensive disease still had a significant association with IKBL+738(C). The difference between the 2 groups of patients was statistically significant (13.7% vs. 1.7% in patients with distal disease; odds ratio, 9.25; P = 0.01).
  
  
  CONCLUSIONS
  HLA-DRB1(*)0103 is associated with susceptibility to ulcerative colitis, and IKBL+738(C) marks a propensity to extensive and more severe disease.
authors: Department of Immunology, Hospital Clinico San Carlos, Madrid, Spain. egomezdela@hcsc.insalud.es
authors: E G
authors: EG
authors: de la Concha
authors: M
authors: M
authors: Fernandez-Arquero
authors: G
authors: G
authors: Lopez-Nava
authors: E
authors: E
authors: Martin
authors: R J
authors: RJ
authors: Allcock
authors: L
authors: L
authors: Conejero
authors: J G
authors: JG
authors: Paredes
authors: M
authors: M
authors: Diaz-Rubio
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000483:Alleles; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000503:physiopathology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012016:Reference Values; D012720:Severity of Illness Index
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; C120111:NFKBIL1 protein, human