The critical region for Behcet disease in the human major histocompatibility complex is reduced to a 46-kb segment centromeric of HLA-B, by association analysis using refined microsatellite mapping

The HLA-B51 allele is known to be associated with Behcet disease. Recently, we found a higher risk for Behcet disease in the MICA gene, 46 kb centromeric of HLA-B, by investigation of GCT repetitive polymorphism within exon 5 of MICA. The pathogenic gene causing Behcet disease, however, has remained uncertain. Here, eight polymorphic microsatellite markers, distributed over a 300-kb region surrounding the HLA-B locus, were subjected to association analysis for Behcet disease. Statistical studies of associated alleles detected on each microsatellite locus showed that the pathogenic gene for Behcet disease is most likely found within a 46-kb segment between the MICA and HLA-B genes. The results of this mapping study, and the results of an earlier study of ours, suggest that MICA is a strong candidate gene for the development-of Behcet disease.