According to the researchers, including Daniel Eriksson from the Karolinska Institutet in Sweden, this novel genetic association could pave the way for early interventions and personalised treatment of an incurable condition. The rarity of Addison's disease has until now made scanning of the whole genome for clues to the disease's genetic origins difficult, as this method normally requires many thousands of study participants, said the study, published in the journal Nature.
However, by combining the world's two largest Addison's disease registries the research team were able to identify strong genetic signals associated with the disease. Most of them are directly involved in the development and functioning of the human immune system including specific molecular types in the so-called HLA-region (this is what makes matching donors and recipients in organ transplants necessary) and two different types of a gene called AIRE (which stands for AutoImmune Regulator).
AIRE is a key factor in shaping the immune system by removing self-reacting immune cells, the researchers said. Variants of AIRE, such as the ones identified in this study, could compromise this elimination of self-reacting cells, which could lead to an autoimmune attack later in life, they added.
Knowing what predisposes people to develop Addison's disease opens up the possibilities of determining the molecular repercussions of the predisposing genetic variation (currently ongoing in Prof Husebye's lab). The fact that it is now feasible to map the genetic risk profile of an individual also means that personalised treatment aimed at stopping and even reversing the autoimmune adrenal destruction can become a feasible option in the future, the researchers said.