PMID- 16116311
OWN - NLM
STAT- MEDLINE
DCOM- 20051122
LR  - 20190513
IS  - 1078-0998 (Print)
IS  - 1078-0998 (Linking)
VI  - 11
IP  - 9
DP  - 2005 Sep
TI  - A recombined haplotype in the major histocompatibility region contains a cluster 
      of genes conferring high susceptibility to ulcerative colitis in the Spanish 
      population.
PG  - 785-91
AB  - 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.
FAU - Fernandez, Laura
AU  - Fernandez L
AD  - Department of Clinical Immunology, Hospital Clinico San Carlos, Madrid, Spain.
FAU - Nunez, Concepcion
AU  - Nunez C
FAU - Mendoza, Juan Luis
AU  - Mendoza JL
FAU - Urcelay, Elena
AU  - Urcelay E
FAU - Fernandez-Arquero, Miguel
AU  - Fernandez-Arquero M
FAU - Taxonera, Carlos
AU  - Taxonera C
FAU - Diaz-Rubio, Manuel
AU  - Diaz-Rubio M
FAU - de la Concha, Emilio G
AU  - de la Concha EG
FAU - Martinez, Alfonso
AU  - Martinez A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Case-Control Studies
MH  - Colitis, Ulcerative/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Male
MH  - Odds Ratio
MH  - Polymorphism, Genetic
MH  - Spain
EDAT- 2005/08/24 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/08/24 09:00
PHST- 2005/08/24 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/08/24 09:00 [entrez]
AID - 00054725-200509000-00001 [pii]
AID - 10.1097/01.mib.0000179210.96025.23 [doi]
PST - ppublish
SO  - Inflamm Bowel Dis. 2005 Sep;11(9):785-91. doi: 
      10.1097/01.mib.0000179210.96025.23.