title: Strong protective effect of DR3 against ulcerative colitis in the Spanish population.
abstract: OBJECTIVE
  Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. Major histocompatibility complex (MHC) on the short arm of human chromosome 6 has been thoroughly studied as a susceptibility locus. However, one of the strongest MHC associations found, that of HLA-DR3 with UC protection, has not been observed in all populations. Our aim in the present study was to evaluate this negative association in a large cohort of Spanish UC patients and controls, and to try to elucidate which, if any, of the diverse DR3 haplotypes (identified by TNFa and b microsatellites, located in the MHC class III region) is most tightly associated (negatively) with the disease.
  
  
  METHODS
  A total of 537 UC patients and 748 healthy controls from Spain were included in the present study. Low-resolution DR genotyping was performed by PCR and hybridization with allele-specific oligonucleotide probes. TNFa and b microsatellites were studied in a subset of samples (279 UC patients and 503 healthy controls) by PCR followed by capillary electrophoresis. DR-TNFa-TNFb haplotypes were estimated by the expectation-maximization algorithm and comparisons were performed by a chi2 test.
  
  
  RESULTS
  After a stepwise procedure, the only DR alleles significantly associated with the disease were DR3 (very strongly, protection) and DR4 (weakly, protection). The strong protective effect of DR3 was evenly distributed among the haplotypes DR3-TNFa1b5, DR3-TNFa2b3, and DR3-TNFother.
  
  
  CONCLUSIONS
  Our results confirm the strong protective effect of DR3 in our population, and suggest that the relevant protective gene is located centromeric to TNFa and TNFb markers in the MHC region.
authors: IBD Unit, Hospital Virgen de las Nieves, Granada, Spain.
authors: María
authors: M
authors: Gómez-García
authors: Javier
authors: J
authors: Oliver
authors: Ana
authors: A
authors: Márquez
authors: Juan L
authors: JL
authors: Mendoza
authors: Miguel Angel
authors: MA
authors: López-Nevot
authors: Miguel
authors: M
authors: Fernández-Arquero
authors: María F
authors: MF
authors: González-Escribano
authors: Manuel
authors: M
authors: Díaz-Rubio
authors: Emilio G
authors: EG
authors: de la Concha
authors: Elena
authors: E
authors: Urcelay
authors: Javier
authors: J
authors: Martín
authors: Alfonso
authors: A
authors: Martínez
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D017422:Sequence Analysis, DNA; D013030:Spain
chemical_list: D015803:HLA-DR3 Antigen