Journal article
Mapping the HLA association in Behcet's disease: A role for tumor necrosis factor polymorphisms?
Arthritis & Rheumatism, Vol.48(3), pp.807-813
2003
Abstract
Objective. Experimental evidence suggests that inappropriate regulation of tumor necrosis factor α (TNFα) may play a role in the pathogenesis of Behçet's disease (BD). This is supported by recent reports high-lighting the efficacy of anti-TNFα agents in the treatment of this disease. The TNF gene is encoded in the class III region of the HLA complex adjacent to HLA-B. This genetic proximity to a gene that is already widely implicated in disease susceptibility led us to investigate the association between TNF promoter polymorphisms and susceptibility to BD. Methods. We studied 133 UK white Caucasoid patients with BD and 354 healthy controls. We attempted to dissect the contribution of individual polymorphisms in this gene-dense region by linkage disequilibrium mapping across 6 adjacent genes.
Results. We report a novel association with the TNF promoter allele TNF-1031C. Subsequent analysis identified 2 extended HLA haplotypes associated with BD. One of them contained the previously recognized susceptibility gene HLA-B*51, while the other was defined by HLA-B*5701. Both of these haplotypes contained the TNF promoter polymorphism -1031C, an allele that was associated with disease even in individuals who did not carry either HLA-B*51 or HLA-B*5701.
Conclusion. The TNF-1031C allele is independently associated with susceptibility to BD in Caucasoid patients. Further studies will be required to determine the functional effects of this polymorphism, its influence in disease pathogenesis, and its role in other ethnic groups.
Details
- Title
- Mapping the HLA association in Behcet's disease: A role for tumor necrosis factor polymorphisms?
- Authors/Creators
- T. Ahmad (Author/Creator) - University of OxfordG.R. Wallace (Author/Creator) - St Thomas' HospitalT. James (Author/Creator) - Calderdale Royal HospitalM. Neville (Author/Creator) - University of OxfordM. Bunce (Author/Creator) - Biotech (Brazil)K. Mulcahy-Hawes (Author/Creator) - University of OxfordA. Armuzzi (Author/Creator) - University of OxfordJ. Crawshaw (Author/Creator) - University of OxfordF. Fortune (Author/Creator) - St James's University HospitalR. Walton (Author/Creator) - University of OxfordM.R. Stanford (Author/Creator) - St Thomas' HospitalK.I. Welsh (Author/Creator) - Lung InstituteS.E. Marshall (Author/Creator) - Wright-Fleming Institute, St. Mary's Hospital, London, UKD.P. Jewell (Author/Creator) - University of Oxford
- Publication Details
- Arthritis & Rheumatism, Vol.48(3), pp.807-813
- Publisher
- Wiley-Blackwell
- Identifiers
- 991005542940507891
- Copyright
- © 2003 by the American College of Rheumatology
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.36 Ophthalmology
- 1.36.1207 Behcet's Disease
- Web Of Science research areas
- Rheumatology
- ESI research areas
- Clinical Medicine