Association of genetic polymorphisms and autoimmune Addison’s disease

Abstract

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.

Keywords::

• 21-hydroxylase autoantibody
• CTLA-4
• endogenous retrovirus
• HLA
• MHC
• MHC2TA
• MIC gene
• prediction
• primary adrenal insufficiency
• vitamin D receptor

Financial & competing interests disclosure

The research activity of the authors is supported by grants from Fondazione Cassa di Risparmio di Perugia, Perugia, Italy and by the EURADRENAL: pathophysiology and natural course of autoimmune adrenal failure in Europe (Grant 201167). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.