Badenhoop Klaus
Medizinische Klinik I, Klinikum der J.W.Goethe-Universität Frankfurt am Main.
Z Arztl Fortbild Qualitatssich. 2004 May;98 Suppl 5:13-5.
Autoimmune disorders of the thyroid such as Graves' disease and Hashimoto's thyroiditis are the most common autoimmune diseases in the Western world. The frequent occurrence of both diseases in members of the same family indicates the influence of common genetic factors generally predisposing to thyroid autoimmunity. Common susceptibility loci have been mapped to the HLA region on chromosome 6p21 (HLA DR, HLA DQ), to chromosome 2q33 (CTLA4) and possibly to chromosome 8q24 (thyroglobulin). Additional susceptibility is conferred by genomic variants of the vitamin D system (vitamin D receptor and CYP1 alpha hydroxylase). Since these polymorphisms prevail also in healthy relatives they are necessary but not sufficient cofactors. The higher prevalence of thyroid autoimmune disease in women cannot be explained by susceptibility genes. The observation of microchimerisms in thyroid tissue might explain that an immunisation by fetal-maternal interaction can lead to thyroid autoimmunity in HLA risk combinations.
甲状腺自身免疫性疾病,如格雷夫斯病和桥本甲状腺炎,是西方世界最常见的自身免疫性疾病。同一家族成员中这两种疾病的频繁发生表明,通常易患甲状腺自身免疫性疾病的共同遗传因素具有影响作用。常见的易感基因座已被定位到6号染色体p21区域的HLA区域(HLA DR、HLA DQ)、2号染色体q33区域(CTLA4),可能还有8号染色体q24区域(甲状腺球蛋白)。维生素D系统的基因组变异(维生素D受体和CYP1α羟化酶)也赋予了额外的易感性。由于这些多态性在健康亲属中也普遍存在,它们是必要但不充分的辅助因素。女性甲状腺自身免疫性疾病的较高患病率不能用易感基因来解释。在甲状腺组织中观察到微嵌合体现象,这可能解释了胎儿与母体相互作用引发的免疫反应如何在HLA风险组合中导致甲状腺自身免疫性疾病。