Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL.
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.
de la Concha
E G
EG
Department of Immunology, Hospital Clinico San Carlos, Madrid, Spain. egomezdela@hcsc.insalud.es
Fernandez-Arquero
M
M
Lopez-Nava
G
G
Martin
E
E
Allcock
R J
RJ
Conejero
L
L
Paredes
J G
JG
Diaz-Rubio
M
M
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
D048868:Adaptor Proteins, Signal Transducing; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; C120111:NFKBIL1 protein, human