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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 119; no. 6; p. 1491
• Main Authors: de la Concha, E G, Fernandez-Arquero, M, Lopez-Nava, G, Martin, E, Allcock, R J, Conejero, L, Paredes, J G, Diaz-Rubio, M
• Format: Journal Article
• Language: English
• Published: United States 01.12.2000
• Subjects: Adult; Alleles; Colitis, Ulcerative - genetics; Colitis, Ulcerative - physiopathology; Gene Frequency; Genetic Predisposition to Disease - genetics; Histocompatibility Antigens Class II - genetics; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Major Histocompatibility Complex - genetics; Polymorphism, Genetic - genetics; Reference Values; Severity of Illness Index
• ISSN: 0016-5085
• DOI: 10.1053/gast.2000.20258

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. 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. 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). HLA-DRB1(*)0103 is associated with susceptibility to ulcerative colitis, and IKBL+738(C) marks a propensity to extensive and more severe disease.