Association analysis between the MIC-A and HLA-B alleles in Japanese patients with Behcet's disease

Objective. Behcet's disease is known to be strongly associated with HLA-B51 in many different ethnic groups, Recently, by association analysis using r efined microsatellite mapping, the critical region for Behcet's disease was identified as a 46-kb segment centromeric to the HLA-B gene. No expressed gene has been detected in this segment to date except the MIG-A (major hist ocompatibility complex class I chain-related gene A) and HLA-B genes. The p resent study was undertaken to analyze allelic distribution of the MIG-A ge ne among Japanese patients with Behcet's disease. Methods. Ninety-five Japanese patients with Behcet's disease and 116 ethnic ally matched healthy controls were enrolled in this study. MIG-A genotyping was performed by direct sequencing of polymerase chain reaction products f rom exons 2, 3, and 4 of the MIG-A gene, using an automated DNA sequencer. Results. The MIC-A009 allele was significantly more frequent in the patient group (69.5%) compared with the healthy controls (31.0%) (relative risk 5. 06, corrected P = 0.00000024), In stratification analysis on the confoundin g effect of MIC-A009 on HLA-B*51 association and vice versa, Behcet's disea se was distinctively associated only with HLA-B*51, Further, MIC-A009 was f ound to be strongly associated not only with HLA-B51, but also with HLA-B52 , which was not increased in the patient group to any degree. Conclusion. These results imply that the real disease susceptibility gene i nvolved in the development of Behcet's disease is the HLA-B*51 allele itsel f and that the significant increase of the MIC-A009 allele in the patient g roup results Secondarily from a strong linkage disequilibrium with HLA-B*51 .