Honda K, Tamai H, Morita T, Kuma K, Nishimura Y, Sasazuki T
Department of Genetics, Faculty of Medicine, Kyushu University, Fukuoka Japan.
J Clin Endocrinol Metab. 1989 Dec;69(6):1268-73. doi: 10.1210/jcem-69-6-1268.
To investigate genetic factors involved in the pathogenesis of Hashimoto's thyroiditis (HT; goitrous autoimmune thyroiditis), HLA class I and class II antigens were analyzed in both seropositive HT (99 patients) and seronegative HT (43 patients). The frequency of HLA-DRw53 antigen was increased significantly in both seropositive HT (antigen frequency, 0.83; relative risk, 33.3; P less than 0.0002; corrected P less than 0.001) and seronegative HT (antigen frequency, 0.81; relative risk, 3.02; P less than 0.01; corrected P less than 0.05). The etiological fraction values for HLA-DRw53 in seropositive HT and seronegative HT were 0.58 and 0.54, respectively. An increased frequency of HLA-DQw4 and a decreased frequency of HLA-DQw1 were observed in patients with seronegative HT. These data suggest that susceptibility to HT is primarily associated with HLA-DRw53 and that HLA-DQ alleles may control the production of autoantibodies to the thyroid gland. The mode of inheritance of disease susceptibility for HT (controlled by a major gene in linkage disequilibrium with HLA-DRw53) was investigated by the method of Thomson and Bodmer, and it was suggested that disease susceptibility was inherited in a dominant manner.
为研究参与桥本甲状腺炎（HT；甲状腺肿性自身免疫性甲状腺炎）发病机制的遗传因素，对血清学阳性HT患者（99例）和血清学阴性HT患者（43例）的HLAⅠ类和Ⅱ类抗原进行了分析。血清学阳性HT患者（抗原频率为0.83；相对危险度为33.3；P＜0.0002；校正后P＜0.001）和血清学阴性HT患者（抗原频率为0.81；相对危险度为3.02；P＜0.01；校正后P＜0.05）中HLA - DRw53抗原的频率均显著增加。血清学阳性HT和血清学阴性HT中HLA - DRw53的病因分值分别为0.58和0.54。在血清学阴性HT患者中观察到HLA - DQw4频率增加和HLA - DQw1频率降低。这些数据表明，HT易感性主要与HLA - DRw53相关，且HLA - DQ等位基因可能控制甲状腺自身抗体的产生。采用汤姆森和博德默的方法研究了HT疾病易感性的遗传模式（由与HLA - DRw53处于连锁不平衡的一个主基因控制），结果提示疾病易感性以显性方式遗传。
