Mapping the HLA association in Behçet's disease: a role for tumor necrosis factor polymorphisms?

Authors: Ahmad, Tariq  Wallace, Graham R  James, Teifi  Neville, Matt  Bunce, Mike  Mulcahy-Hawes, Kim  Armuzzi, Alessandro  Crawshaw, Jonathan  Fortune, Farida  Walton, Robert  Stanford, Miles R  Welsh, Ken I  Marshall, Sara E  Jewell, Derek P 
Citation: Ahmad T, etal., Arthritis Rheum. 2003 Mar;48(3):807-13.
Pubmed: (View Article at PubMed) PMID:12632436
DOI: Full-text: DOI:10.1002/art.10815


OBJECTIVE: Experimental evidence suggests that inappropriate regulation of tumor necrosis factor alpha (TNF alpha) may play a role in the pathogenesis of Behçet's disease (BD). This is supported by recent reports highlighting the efficacy of anti-TNF alpha 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.

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CRRD Object Information
CRRD ID: 12904036
Created: 2017-05-15
Species: All species
Last Modified: 2017-05-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.