title: A recombined haplotype in the major histocompatibility region contains a cluster of genes conferring high susceptibility to ulcerative colitis in the Spanish population.
abstract: 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.
authors.affiliation: Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández
authors.forename: Concepción
authors.initials: C
authors.lastname: Núñez
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Mendoza
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: Carlos
authors.initials: C
authors.lastname: Taxonera
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
mesh_terms: 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
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains