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

BACKGROUND & AIMS: 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.