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 -DRB40101 (DR53) (p < 0.01, RR = 2.03, EF = 0.61 and p < 0.0001, RR = 4.48, EF = 0.69, respectively). Although HLA-DR8, -DRB10403, -DQA03, and -DQB10303 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 -DRB40101 in the Japanese population. Ninety-seven percent of the patients (69 out of 71) were positive for HLA-A2 or -DRB40101 compared to 79% in controls (RR = 8.7, p < 0.0005). The combination of HLA-A2 and -DRB40101 showed higher OR of risk for HT (OR = 12.8) than HLA-A2 (OR = 7.3) or DRB40101 (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 DQA10102 was significantly decreased in the patient group, suggesting that DQA10102 might confer resistance to HT.