Nine gene variants have been found to increase the risk of developing Addison’s disease, according to the largest genetic study to date on patients with the disorder.
Researchers at Karolinska Institutet, Sweden, and Bergen University, Norway, completed the first genetic study of the disease that spans the entire human genome and found variants of nine genes, many of which are central to the human immune system, induce a higher risk of developing the disease.
For the research, which is published in Nature Communications, the scientists recruited patients from the Swedish and Norwegian Addison registries, and isolated DNA from 1,223 people with autoimmune Addison’s disease and 4,097 healthy geographically matched individuals as the control group.
When they analysed almost seven million gene variants, they found several that were significantly more common in people with Addison’s disease and some have previously been associated with autoimmune diseases.
But one, the AIRE gene, which is essential to the ability of T cells to learn to tolerate endogenous proteins, was specifically linked to Addison’s disease.
People with Addison’s disease were found to produce an AIRE protein with an additional cysteine more often than those who do not have the disorder.
Study leader Dr Daniel Eriksson, of the Department of Medicine, Solna, Karolinska Institutet, said: “Many autoimmune diseases have several features in common when it comes to genetic predispositions that govern the function of the immune system, but in this study we also identified distinctive genetic associations that are unique to Addison’s disease. This is a step forward in our understanding of its pathogenesis.”
Eriksson D, Røyrvik EC, Aranda-Guillén M et al. GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility. Nature Communications 11 February 2021; doi:10.1038/s41467-021-21015-8
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