HLA-A AND HLA-DRB4 GENES IN CONTROLLING THE SUSCEPTIBILITY TO HASHIMOTOS-THYROIDITIS

HLA-linked genetic factors involved in the pathogenesis of HT were stu died 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, -DQB2, 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 < 0.00 01, RR = 4.48, EF = 0.69, respectively). Although HLA-DR8, -DRB10403, -DQA103, and -DQB1*0303 were statistically more prevalent in the pat ient group than in the controls, these associations were presumably du e to the strong linkage disequilibria of these alleles with HLA-A2 or -DRB40101 in the Japanese population. Ninety-seven percent of the pat ients (63 out of 71) were positive for HLA-A2 or -DRB40101 compared t o 79% in controls (RR = 8.7, p < 0.0005). The combination of HLA-A2 an d -DRB40101 showed higher OR of risk for HT (OR = 12.8) than HLA-A2(O R = 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 susce ptibility to HT. On the other hand, the frequency of DQA10102 was sig nificantly decreased in the patient group, suggesting that DQA10102 m ight confer resistance to HT.