Ban Yoshiyuki, Tomer Yaron
Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Pediatr Endocrinol Rev. 2005 Sep;3(1):20-32.
The autoimmune thyroid diseases (AITD) include Graves' disease (GD) which manifests in hyperthyroidism and Hashimoto's thyroiditis (HT), manifesting as hypothyroidism. Genetic susceptibility in combination with external factors (e.g. dietary iodine) are believed to initiate the autoimmune response to thyroid antigens in AITD. Indeed, there is solid epidemiological data to support a strong genetic influence on the etiology of AITD including family and twin studies. Recently, there has been significant progress toward the identification of the AITD susceptibility genes. Several loci (genetic regions) that are linked with AITD have been mapped and in some of these loci putative AITD susceptibility genes have been identified. Some of these loci predispose to a single phenotype (GD or HT), while other loci are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg) and it is likely that the final disease phenotype is a result of an interaction between these loci, as well as environmental influences.
自身免疫性甲状腺疾病(AITD)包括表现为甲状腺功能亢进的格雷夫斯病(GD)和表现为甲状腺功能减退的桥本甲状腺炎(HT)。遗传易感性与外部因素(如膳食碘)相结合被认为会引发AITD中针对甲状腺抗原的自身免疫反应。事实上,有确凿的流行病学数据支持遗传因素对AITD病因有很强的影响,包括家族研究和双胞胎研究。最近,在鉴定AITD易感基因方面取得了重大进展。几个与AITD相关的基因座(遗传区域)已被定位,并且在其中一些基因座中已鉴定出推定的AITD易感基因。其中一些基因座易患单一表型(GD或HT),而其他基因座在两种疾病中都常见,这表明GD和HT存在共同的遗传易感性。推定的GD和HT易感基因包括免疫调节基因(如HLA、CTLA-4)和甲状腺特异性基因(如TSHR、Tg),最终的疾病表型可能是这些基因座之间相互作用以及环境影响的结果。