HLA-A and -DRB4 genes in controlling the susceptibility to Hashimoto's thyroiditis.

HLA-linked genetic factors involved in the pathogenesis of HT were studied in 71 patients with HT by serologic typing for HLA-A, -B, -C, -DR, and -DQ specificities and by DNA typing for HLA-DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, AND -DPB1 genes using the PCR-SSOP method. Typing results demonstrated significant positive associations of HT with HLA-A2 and -DRB4*0101 (DR53) (p < 0.01, RR = 2.03, EF = 0.61 and p < 0.0001, RR = 4.48, EF = 0.69, respectively). Although HLA-DR8, -DRB1*0403, -DQA*03, and -DQB1*0303 were statistically more prevalent in the patient group than in the controls, these associations were presumably due to the strong linkage disequilibria of these alleles with HLA-A2 or -DRB4*0101 in the Japanese population. Ninety-seven percent of the patients (69 out of 71) were positive for HLA-A2 or -DRB4*0101 compared to 79% in controls (RR = 8.7, p < 0.0005). The combination of HLA-A2 and -DRB4*0101 showed higher OR of risk for HT (OR = 12.8) than HLA-A2 (OR = 7.3) or DRB4*0101 (OR = 7.5) alone. These observations suggest that at least two loci, HLA-A and HLA-DRB4 together, may control the susceptibility to HT. On the other hand, the frequency of DQA1*0102 was significantly decreased in the patient group, suggesting that DQA1*0102 might confer resistance to HT.