ESPE Yearbook of Paediatric Endocrinology

Nat Rev Endocrinol. 2022; 18(7): 399-412. PMID: 35411072https://pubmed.ncbi.nlm.nih.gov/35411072/

Brief Summary: This review summarizes the current knowledge and understanding of the genetics of autoimmune Addison disease and its position in the wider field of autoimmune disorders.

Autoimmune Addison’s disease (AAD) is caused by the destruction of the adrenal cortex causing deficiencies of certain adrenal steroids. Patients with AAD require life-long replacement therapy with corticosteroids. It has long been recognized that AAD has an important genetic component and attempts at identifying genetic variants that may explain individual predisposition have been performed over the last two decades. This review summarizes the current knowledge and recent advances regarding the genetic etiology of autoimmune Addison’s disease. The authors highlight that previous studies on this topic had problems with reproducibility, an issue that might be solved with more unbiased genome-wide association studies. Furthermore, the review thoroughly describes known AAD risk loci, both from candidate gene and genome-wide association studies. Plausible risk loci indicate that AAD is primarily a T cell-mediated disease, with affected individuals predisposed to it because they carry common variants that individually are only mildly deleterious on autoimmunity. Many AAD risk loci overlap with those published for other autoimmune diseases, such as type 1 diabetes, indicating that the diseases have similar pathogenic mechanisms.

In summary, the review provides a good overview regarding the genetic etiology of AAD. The authors describe the associations between plausible risk loci and disease mechanisms, and provide useful suggestions about future studies to determine the etiology of AAD.