Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, Via E. Dal Pozzo, 06126 Perugia, Italy.
Expert Rev Clin Immunol. 2008 Jul;4(4):441-56. doi: 10.1586/1744666X.4.4.441.
Autoimmune Addison's disease (AAD) is a complex genetic disease that results from the interaction of a predisposing genetic background with as yet unknown environmental factors. The disease is marked by the appearance of circulating autoantibodies against steroid 21-hydroxylase. Mutations of the autoimmune regulator gene are responsible for the so-called autoimmune polyendocrine syndrome type I (APS I), of which AAD is a major disease component. Among genetic factors for isolated AAD and APS II, a major role is played by HLA class II genes: HLA-DRB1 0301-DQA1 0501-DQB1 0201 and DRB1 04-DQA1 0301-DQB1 0302 are positively, and RB1 0403 is negatively, associated with a genetic risk for AAD. The MHC class I chain-related gene A allele 5.1 is strongly and positively associated with AAD. Other gene polymorphisms contributing to genetic risk for AAD are MHC2TA, the gene coding for class II transactivator, the master regulator of class II expression, cytotoxic T lymphocyte antigen-4, PTPN22 and the vitamin D receptor.
自身免疫性肾上腺皮质功能减退症（AAD）是一种复杂的遗传性疾病，由易感遗传背景与尚未明确的环境因素相互作用引起。该疾病的特征是存在针对类固醇 21-羟化酶的循环自身抗体。自身免疫调节基因的突变导致所谓的自身免疫性多内分泌腺综合征 1 型（APS I），其中 AAD 是主要疾病组成部分。在孤立性 AAD 和 APS II 的遗传因素中，HLA Ⅱ类基因起着重要作用：HLA-DRB1 0301-DQA1 0501-DQB1 0201 和 DRB1 04-DQA1 0301-DQB1 0302 与 AAD 的遗传风险呈正相关，而 RB1 0403 与 AAD 的遗传风险呈负相关。MHC Ⅰ类链相关基因 A 等位基因 5.1 与 AAD 呈强烈正相关。其他与 AAD 的遗传风险相关的基因多态性包括 MHC2TA、编码 II 类转录激活子的基因、II 类表达的主调控因子、细胞毒性 T 淋巴细胞抗原-4、PTPN22 和维生素 D 受体。
