Department of Clinical Science, University of Bergen, Bergen, Norway.
K.G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.
Nat Rev Endocrinol. 2022 Jul;18(7):399-412. doi: 10.1038/s41574-022-00653-y. Epub 2022 Apr 11.
Autoimmune Addison disease is an endocrinopathy that is fatal if not diagnosed and treated in a timely manner. Its rarity has hampered unbiased studies of the predisposing genetic factors. A 2021 genome-wide association study, explaining up to 40% of the genetic susceptibility, has revealed new disease loci and reproduced some of the previously reported associations, while failing to reproduce others. Credible risk loci from both candidate gene and genome-wide studies indicate that, like one of its most common comorbidities, type 1 diabetes mellitus, Addison disease is primarily caused by aberrant T cell behaviour. Here, we review the current understanding of the genetics of autoimmune Addison disease and its position in the wider field of autoimmune disorders. The mechanisms that could underlie the effects on the adrenal cortex are also discussed.
自身免疫性艾迪生病是一种内分泌疾病，如果不能及时诊断和治疗，可能致命。由于其罕见性，阻碍了对其易感遗传因素的无偏研究。2021 年的一项全基因组关联研究解释了高达 40%的遗传易感性，揭示了新的疾病位点，并再现了一些先前报道的关联，但未能再现其他关联。来自候选基因和全基因组研究的可信风险位点表明，与最常见的合并症之一 1 型糖尿病一样，艾迪生病主要是由异常 T 细胞行为引起的。在这里，我们回顾了自身免疫性艾迪生病遗传学的现有认识及其在自身免疫性疾病更广泛领域中的地位。还讨论了可能导致肾上腺皮质效应的机制。
