Association Analysis of the Polymorphism of Human Leukocyte Antigen-A, -B and -E Gene with Behcet's Disease in Japanese Cohort Using Sequencing-Based Typing Method

Behcet’s disease (BD) is a chronic inflammatory autoimmune disease and strongly associated with human leukocyte antigen (HLA) gene such as HLA-B and -A. To determine the association of the HLA-A, HLA-B and HLA-E alleles with BD in Japanese cohort as well as other cohorts, we performed sequencing-based typing method in 382 BD cases and healthy controls. Then, we analyzed the association of these alleles with BD. Our results indicated that HLA-B*51 is strongly associated with BD in Japanese cohort (Allelic model’s P value and OR are 4.59x10-26 and 4.59, respectively. Dominant model’s P value and OR are 2.1x10-24 and 5.32, respectively), while HLA-A*26 is also significantly associated with BD (Allelic model’s P value and OR are 5.3x10-5 and 1.80, respectively. Dominant model’s P value and OR are 8.6x10-6 and 2.06, respectively.). HLA-E*01:01 was not observed to have any significant association with BD. We also obtained the available data sets of Chinese and Japanese genome sequence from public data base and then, analyzed each Linkage disequilibrium (LD) structure using SNPs in HLA-A, -B and –E region. The pattern of LD including HLA-E was different between two cohorts. Collectively, we suggested that HLA-B*51 and HLA-A*26 are associated with BD in Japanese cohort as well as another cohort and that HLA-E*01:01 is not associated with BD. Our data suggest that LD structure of the region including HLA-E depends on a type of ethnic group even among Asian ethnic group.