A recombined haplotype in the major histocompatibility region contains a cluster of genes conferring high susceptibility to ulcerative colitis in the Spanish population.
BACKGROUND
The most consistently described associations in ulcerative colitis (UC) have been with human leukocyte antigen (HLA) class II alleles. Our aim was to look for associations among distinct genetic polymorphisms in the major histocompatibility complex (MHC) that might play a role in determining the susceptibility to UC and especially to the extensive form of the disease.


METHODS
A case-control study was performed with a total of 253 patients with UC and 315 healthy controls recruited from a single Spanish center. All the samples and 4 cell lines carrying DRB1*0103 or DRB1*1501 alleles were typed for the HLA-DRB1 class II gene and for a panel of HLA class III markers (D6S273, BAT_2, TNFa, b, c, d, e, IKBL+738, MICA).


RESULTS
The frequency of the alleles DRB1*0103, IKBL+738(C) (extending our previous results) and BAT_2-8 (newly typed) was increased in patients compared with controls (P=0.00001, odds ratio [OR]=5.90; P=0.002, OR=2.42; and P=0.0001, OR=3.04, respectively), and these associations were greatest in patients with extensive disease compared with patients with distal disease (P=0.02, OR=2.53; P=0.002, OR=3.06; and P=0.03, OR=2.08, respectively). The allelic combination DRB1*0103/D6S273-5/BAT_2-8/TNFa11b4c1d3e3/IKBL+738(C)/MICA5.1 that includes the telomeric class III markers of the 7.1 ancestral haplotype is highly increased in patients with UC (P=0.0001, OR=10.57), especially in those with the extensive form of the disease (P=0.02, OR=3.41 extensive versus distal).


CONCLUSIONS
The above-mentioned pattern, most likely formed by recombination of the telomeric fragment of the MHC 7.1 ancestral haplotype, seems to be the most important genetic determinant of susceptibility to the extensive form of UC in our population.
Fernández
Laura
L
Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain.
Núñez
Concepción
C
Mendoza
Juan Luis
JL
Urcelay
Elena
E
Fernández-Arquero
Miguel
M
Taxonera
Carlos
C
Díaz-Rubio
Manuel
M
de la Concha
Emilio G
EG
Martínez
Alfonso
A
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D013030:Spain
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains