Strong protective effect of DR3 against ulcerative colitis in the Spanish population.
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.
Gómez-García
María
M
IBD Unit, Hospital Virgen de las Nieves, Granada, Spain.
Oliver
Javier
J
Márquez
Ana
A
Mendoza
Juan L
JL
López-Nevot
Miguel Angel
MA
Fernández-Arquero
Miguel
M
González-Escribano
María F
MF
Díaz-Rubio
Manuel
M
de la Concha
Emilio G
EG
Urcelay
Elena
E
Martín
Javier
J
Martínez
Alfonso
A
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
D015803:HLA-DR3 Antigen