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

Tariq Ahmad, Graham R. Wallace, Teifi James, Matt Neville, Mike Bunce, Kim Mulcahy-Hawes, Alessandro Armuzzi, Jonathan Crawshaw, Farida Fortune, Robert Walton, Miles R. Stanford, Ken I. Welsh, Sara E. Marshall, Derek P. Jewell

    Research output: Contribution to journalArticlepeer-review

    122 Citations (Scopus)

    Abstract

    Objective. Experimental evidence suggests that inappropriate regulation of tumor necrosis factor ? (TNF?) may play a role in the pathogenesis of Behçet's disease (BD). This is supported by recent reports highlighting the efficacy of anti-TNF? 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.
    Original languageEnglish
    Pages (from-to)807-813
    Number of pages7
    JournalArthritis & Rheumatism
    Volume48
    Issue number3
    DOIs
    Publication statusPublished - Mar 2003

    Fingerprint Dive into the research topics of 'Mapping the HLA association in Behçet's disease: A role for tumor necrosis factor polymorphisms?'. Together they form a unique fingerprint.

    Cite this