scholarly journals GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daniel Eriksson ◽  
◽  
Ellen Christine Røyrvik ◽  
Maribel Aranda-Guillén ◽  
Amund Holte Berger ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Addison’S Disease ◽  
Immunological Tolerance ◽  
Cysteine Residue ◽  
Addison's Disease ◽  
Lymphocyte Function ◽  
Protein Coding ◽  
Complex Inheritance ◽  
Low Prevalence ◽  
Additional Cysteine Residue

AbstractAutoimmune Addison’s disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10−8). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7–4.3), P = 9.0 × 10−25) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35–41% of heritability (h2).

scholarly journals Genome-Wide Association Study Links Autoimmune Addison’s Disease to Break of Central Tolerance

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A167-A168
Author(s):  
Maribel Aranda Guillen ◽  
Ellen Christine Røyrvik ◽  
Daniel Eriksson ◽  
Amund Holte Berger ◽  
Nils Landegren ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Addison’S Disease ◽  
Immunological Tolerance ◽  
Cysteine Residue ◽  
Genome Wide Association ◽  
Addison's Disease ◽  
Central Tolerance ◽  
Genome Wide ◽  
A Genome

Abstract Autoimmune Addison’s disease is the predominant cause of primary adrenal failure, and is highly heritable. The genetic background has remained poorly understood due to the low prevalence and complex inheritance of the disease. We performed a genome-wide association study, which identified nine independent risk loci (P &lt; 5 × 10–8). In addition to novel and previous risk loci involved in lymphocyte functionality, we further associated autoimmune Addison’s disease with two independent protein-coding alterations in the gene Autoimmune Regulator (AIRE). The most striking is the amino-acid substitution p.R471C (rs74203920, OR = 3.4 (2.7–4.3), P = 9.0 × 10–25), which introduces an additional cysteine residue in the zinc-finger motif of the PHD2 domain of AIRE. This unbiased elucidation of the genetic contribution to development of autoimmune Addison’s disease points to the importance of central immunological tolerance, and explains 35–41 percent of heritability.

Addison's disease as a rare cause of chronically elevated transaminases

2004 ◽  
Vol 42 (05) ◽  
Author(s):  
GC Gurakuqi ◽  
V Stadlbauer ◽  
H Warnkross ◽  
M Trauner
Keyword(s):  
Addison’S Disease ◽  
Addison's Disease ◽  
Elevated Transaminases

"STEROID-CELL" ANTIBODY IN ENDOCRINE DISEASES

1974 ◽  
Vol 76 (4) ◽  
pp. 729-740 ◽  
Author(s):  
Peter Kamp ◽  
Per Platz ◽  
Jørn Nerup
Keyword(s):  
Leydig Cells ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Hormone Production ◽  
Cortical Cells ◽  
Endocrine Diseases ◽  
Cell Antibody ◽  
Indirect Immunofluorescence Technique ◽  
Males And Females ◽  
Adrenal Cortical Cells

ABSTRACT By means of an indirect immunofluorescence technique, sera from 116 patients with Addison's disease, an equal number of age and sex matched controls and 97 patients with other endocrine diseases were examined for the occurrence of antibody to steroid-producing cells in ovary, testis and adrenal cortex. Fluorescent staining was observed in the theca cells of growing follicles, the theca lutein cells, testicular Leydig cells and adrenal cortical cells, i. e. cells which contain enzyme systems used in steroid hormone production. The "steroid-cell" antibody was present in 24 % of the patients with idiopathic Addison's disease, equally frequent in males and females, and in 17 % of the patients with tuberculous Addison's disease, but was rarely found in controls, including patients with other endocrine diseases. Female hypergonadotrophic hypogonadism made an exception, since the "steroid-cell" antibody was found in about half the cases with this condition.

P450 side-chain cleavage enzyme autoantibodies in canine Addison's disease

2013 ◽  
pp. 1-1
Author(s):  
Alisdair Boag ◽  
Kerry McLaughlin ◽  
Mike Christie ◽  
Peter Graham ◽  
Harriet Syme ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

A case of addison's disease associated with ankylosing spondylitis

2014 ◽  
Author(s):  
Neslihan Soysal Atile ◽  
Sibel Guldiken ◽  
Fatih Saritas ◽  
Huseyin Celik ◽  
Armagan Tugrul
Keyword(s):  
Ankylosing Spondylitis ◽  
Addison’S Disease ◽  
Addison's Disease

Addison's disease caused by adrenal gland tuberculosis

2016 ◽  
Author(s):  
Antonela Sabati Rajic ◽  
Maja Ivartnik Merkac ◽  
Petra Svetina
Keyword(s):  
Adrenal Gland ◽  
Addison’S Disease ◽  
Addison's Disease
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