Vitamin D receptor genotype is associated with Addison's disease

Objective: Autoinumme Addison's disease is a rare disorder which results from the T cell-mediated destruction of adrenocortical cells. A number of genetic susceptibility markers are shared by Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis. The vitamin D endocrine system has been shown to influence immune regulation. Variants of the nuclear vitamin D receptor (VDR) gene were found to be associated with type 1 diabetes and thyroid autoimmunity amongst others. We therefore investigated the role of VDR polymorphisms in Addison's disease. Design and methods: Patients (n = 95) and controls (n = 220) were genotyped for VDR polymorphisms FAL BsmI, ApaI and TaqI. Results: The 'ff' (13.7% vs 5.5%; P = 0.0243; odds ratio = 2.75) and the 'tt' (28.4% vs 14.1%; P 0.0043; odds ratio = 2.42) genotypes were significantly more frequent in patients than in controls. Furthermore, the Bsml genotype distribution differed significantly between patients and controls (chi(2) = 6.5016 (2 d.f.) P = 0.0387). Conclusions: These data suggest that the VDR genotype is associated with Addison's disease. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.