Localization of the pathogenic gene of Behcet's disease by microsatellite analysis of three different populations

PURPOSE. Behcet's disease (BD) is known to be associated with HLA-BSI in ma ny ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsate llite markers distributed around the HLA-B gene were investigated. The BD p atients studied were of three ethnic origins: Japanese, Greek, or Italian. METHOD. The total group consisted of 172 BD patients, of whom were 95 Japan ese, 55 Greek, and 27 Italian. Eight polymorphic microsatellite markers dis tributed within 1100 kb of the HLA-B gene were analyzed using PCR and subse quent automated fragment detection by fluorescent-based technology. RESULTS. Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, Pc = 0.000014; Gre ek, Pc = 0.00047, Italian, Pc = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, Pc = 0.000000000017; Greek, Pc = 0.00000032; Italian, Pc = 0.0074). In genotypi c differentiation between the patients and controls, only HLA-BSI was found to be significantly associated with BD in all three populations. Stratific ation analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-BSI. CONCLUSIONS. These results suggest that the pathogenic gene of BD is HLA-B5 1 itself and not other genes located in the vicinity of HLA-B.