Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL

Background & Aims: IKBL gene ties telomeric of the tumor necrosis factor cl uster in the central major histocompatibility complex and carries a structu ral polymorphism at position +738. In the Spanish white population, we foun d the IKBL+738(C) allele in haplotypes carrying either HLA-DRBI*1501 or -DR B1*0103. Because these HLA class II alleles may confer susceptibility to ul cerative colitis, we investigated an association between IKBL+738(C) and th is disease. Methods: DNA-based techniques were used to type individual alle les of HLA-DRB1 and IKBL+738. The frequencies of these alleles were compare d among ethnically matched populations comprising 155 patients and 298 cont rols. Results: IKBL+738(C) allele was exclusively increased in patients wit h extensive and/or intractable disease. HLA-DRB1*0103 was the only HLA-DRB1 allele to be significantly increased in frequency in patients with UC comp ared with controls. It was found in patients with extensive and distal dise ase. In the HLA-DRB1*0103negative population, patients with extensive disea se still had a significant association with IKBL+738(C). The difference bet ween 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.