Endocrine Abstracts

Background: Despite a high heritability of Autoimmune Addison’s Disease (AAD), genetic factors contributing to disease development are still not well defined. An association between the p.R471C variant of AIRE gene and AAD was suggested by a genome-wide association study performed by Eriksson et al. in 2021. However, variants within the AIRE gene are conventionally recognised as causing the rare monogenic Autoimmune Polyendocrine Syndrome Type 1 (APS-1), and not the much commoner sporadic AAD or the Autoimmune Polyendocrine Syndrome Type 2 (APS-2).

Methods: We performed allele-discrimination PCR genotyping of the p.R471C variant of AIRE gene (rs74203920) in DNA from 433 AAD patients, 535 patients with Graves’ disease (GD) and 218 local healthy controls.

Results: There was a significant association between AAD and risk T allele of p.R471C variant of AIRE gene when compared to both healthy controls and GNOMAD Non-Finnish Europeans (Table 1) To test whether the effect of rs74203920 was associated with different AAD phenotypes, we checked for difference in sporadic AAD, APS-2 (AAD with autoimmune thyroid disease and/or T1DM) and other autoimmune comorbidities like pernicious anaemia and premature ovarian insufficiency. There was no significant difference between isolated AAD and other autoimmune comorbidities, except T1DM (Table 2).

Conclusion: Our findings support the original suggestion by Eriksson et al. that SNP rs74203920 of AIRE gene is associated with AAD, but not with GD.