The association between HLA-DQA1, HLA-DQB1 and HLA-DRB1 LOCI with graves disease in Thai Population

Human leukocyte antigen (HLA) genes are one of the most important genetic risk factors for susceptibility to various autoimmune diseases including Graves{174} disease (GD). The molecular mechanism of specific HLA association might be due to its role in autoantigen presentation or the ability to select autoreactive T cells. The distribution of HLA DRB1, DQA1 and DQB1 alleles were analyzed in GD patients compared to normal control in order to identify the alleles associated with GD in Thai population. Population-base case-control study was designed using 124 unrelated Thai GD patients and 124 healthy unrelated Thai individuals with similar ethnic and geographic background. Molecular HLA typings were performed using PCR-SSP (sequence specific primers) and PCR-SSOP (sequence specific oligonucleotide probes). The significance of differences between the two groups were analyzed by the chi-square test. The allele frequency of subjects positive for HLA-DRB1*1602 (P = 0.0063; OR = 2.91), DQA1*0102 (P = 0.0028; OR = 1.91) and DQB1* 0502 (P = 0.0074; OR = 1.94) alleles were significantly increased among GD patients. The analysis of DRB1*1602-DQA1*0102-DQB1*0502 haplotype demonstrated that it was also significantly increased in GD patients (P = 0.0209; OR = 2.55). In addition, we found that DRB1*07 and DQA1*0201 alleles were negatively associated with similar OR of 0.25 (P = 0.0065) and DQA1*0601 allele was another protective allele with OR of 0.36 (P = 0.0094). Haplotype analysis demonstrated 2 protective haplotypes. DRB1*07-DQA1*0201-DQB1*0201 haplotype (P = 0.039; OR = 0.32) and HLA-DRB1*12-DQA1*0601-DQB1*0301 haplotype (P = 0.0025; OR = 0.28) was significantly decreased in GD patients. This findings of a significant associated of DRB1*1602-DQA1*0102-DQB1*0502 and HLA-DRB1*12-DQA1*0601-DQB1*0301 alleles and haplotypes in Thai with GD has not been documented in any ethnic group. DRB1*1602-DQA1*0102-DQB1*0502 alleles and haplotype is the marker for genetic susceptibility to GD in Thai population.