Genetic variants in TNF-alpha but not DLG5 are associated with inflammatory bowel disease in a large United Kingdom cohort.
Inflamm Bowel Dis
; 12(3): 178-84, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16534418
ABSTRACT
BACKGROUND:
Genetic variants in DLG5, which encodes a scaffolding protein on chromosome 10q23, and tumor necrosis factor (TNF)-alpha, encoding a proinflammatory cytokine on chromosome 6p, have recently been reported to be associated with inflammatory bowel disease (IBD). We studied these variants to seek evidence of association with IBD in a large independent dataset.METHODS:
We genotyped 1104 unrelated white IBD subjects-496 with Crohn's disease, 512 with ulcerative colitis, and 96 with indeterminate colitis from the Cambridge/Eastern (UK) panel-and 760 healthy control subjects for DLG5_113G/A, DLG5_4136C/A, TNF-857C/T, and TNF-1031T/C polymorphisms. Known Crohn's disease-predisposing variants in CARD15/NOD2 were also genotyped to permit analysis for reported epistatic interactions.RESULTS:
TNF-857 was shown to be associated with IBD overall (P = 0.0079). A formal interaction test showed that TNF-857 is associated equally with ulcerative colitis and Crohn's disease. Neither of the DLG5 alleles, however, was associated with IBD (P = 0.32 and 0.35). Subgroup analysis also failed to show evidence of association between either DLG5 allele or genotype frequencies and ulcerative colitis or Crohn's disease. Stratification of TNF-alpha and DLG5 cases by CARD15 genotype made no significant difference in the strength of associations.CONCLUSIONS:
We have confirmed an association between the TNF-857 promoter polymorphism and IBD in a large independent UK dataset but were unable to replicate an association at the previously reported loci within DLG5. This may reflect heterogeneity between the populations, a smaller effect size than originally predicted, or possibly a false-positive result in the original study. Further fine mapping studies of the TNF promoter region and studies assessing functional consequences of TNF promoter polymorphisms are now required in IBD.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Doenças Inflamatórias Intestinais
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Fator de Necrose Tumoral alfa
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Predisposição Genética para Doença
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Proteínas Supressoras de Tumor
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Proteínas de Membrana
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido