Objectives: Behçet's disease (BD) is a rare, chronic, systemic, inflammatory disorder characterized by recurrent ocular, genital and skin lesions. Although its etiology is still uncertain, an intricate interplay between the environment (e.g. viruses) and the host seem to initiate and/or perpetuate the disease, although its mechanistics remains presently speculative. Since the identification of HLA-B*5101 (and more recently of MICA) as a susceptibility locus for BD, the identification of additional genetic locus/loci, whether inside, or perhaps more importantly outside the MHC has clearly stalled. We hereby present the results of a first genomewide association study (GWAS) of BD.
Methods: 300 Japanese patients with BD and an equal number of controls were recruited. The samples were screened using a dense panel of 23,465 microsatellites (MS) covering the entire genome.
Results: We identified the six best (of a total of 147) positively associated MS with BD. Of these six, two were located within the HLA class I region itself. Although one of these was clearly reminiscent of the association with HLA-B, the second, not in linkage disequilibrium with the former was in the telomeric side of the class I region and remained to be formally identified. In fine, HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to BD’s pathogenesis: HLA-B*5101 and HLA-A*26.
Conclusions: This GWAS highlights the premier genetic susceptibility locus for BD as the MHC itself, wherein reside two independent loci: HLA-B and HLA-A.