CHRONIC ADRENAL INSUFFICIENCY: GENETIC ASPECTS OF THE DISEASE
This review article provides current information on the pathogenetic and genetic features of primary adrenal insufficiency (1-HI) based on the analysis of available scientific articles indexed in PubMed and Web of Science. The aim of this article is to review the immunological and molecular genetic mechanisms of 1-HI development of various genesis. The diversity of etiological causes of adrenal cortical insufficiency has raised the need for the medical community to expand knowledge of proven gene mutations that lead to decreased adrenal function combined with lesions of various organs and systems. This review presents the latest data from the first genome-wide association study (GWAS) of 1-HI of autoimmune origin. The study showed associations of autoimmune 1-HI with risk loci variants PTPN22, CTLA4, LPP, BACH2, SH2B3, SIGLEC5, UBASH3A, and AIRE gene. Four previously unknown loci have been identified: LPP, SH2B3, SIGLEC5 and UBASH3A. 1-HI may be a component of autoimmune polyglandular syndromes type 1 and type 2 with a mutation in the AIRE gene. Despite the achievements of modern science, modern methods of genetic research allowing to establish the diagnosis of 1-HI, to clarify its pathogenetic mechanisms, and to individualize treatment are yet to be introduced into clinical practice.