TY - JOUR T1 - Genetics of Behçet disease inside and outside the MHC JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 747 LP - 754 DO - 10.1136/ard.2009.108571 VL - 69 IS - 4 AU - Akira Meguro AU - Hidetoshi Inoko AU - Masao Ota AU - Yoshihiko Katsuyama AU - Akira Oka AU - Eiichi Okada AU - Ryoji Yamakawa AU - Takenosuke Yuasa AU - Toshihiko Fujioka AU - Shigeaki Ohno AU - Seiamak Bahram AU - Nobuhisa Mizuki Y1 - 2010/04/01 UR - http://ard.bmj.com/content/69/4/747.abstract N2 - Background Behçet disease (BD) is a rare, chronic, systemic, inflammatory disorder characterised by recurrent ocular, genital and skin lesions. Although its aetiology is still uncertain, an intricate interplay between the environment (eg, viruses) and the host seems to initiate and/or perpetuate the disease, although the mechanism remains 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. Objective To carry out a genome-wide 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 The six best (of a total of 147) positively associated MS with BD were identified. Of these six, two were located within the human leucocyte antigen (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. HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to the pathogenesis of BD: HLA-B*5101 and HLA-A*26. Conclusions This GWAS highlights the premier genetic susceptibility locus for BD as the major histocompatibility complex itself, wherein reside two independent loci: HLA-B and HLA-A. ER -