Endocrine Abstracts (2010) 22 P758

Increased frequency of the glucocorticoid receptor gene polymorphisms in patients with autoimmune thyroid diseases

Jadranka Antic1, Milan Petakov1,2, Sanja Ognjanovic1, Neda Dragicevic1, Milan Lakocevic1 & Svetozar Damjanovic1,2

1Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia; 2Medical Faculty, University of Belgrade, Belgrade, Serbia.

Background: Glucocorticoids (GCs) have an important modulatory influence on immune system. GCs accomplish their effects on target tissue through binding to the glucocorticoid receptor (GR). Alterations in glucocorticoid signaling due to polymorphisms of the GR gene may have an impact on the pathophysiology of autoimmune disorders.

Aims/methods: We examined the presence of BclI, N363S, A3669G and ER22/23EK GR gene variants in patients with autoimmune thyroid disorders i.e. primary hypothyroidism due to Hashimoto thyroiditis and Graves hyperthyroidism and healthy control subjects (30 patients, mean age 45.9±2.2 years; 36 patients mean age 36.1±2.1 years; and 221 healthy controls mean age 42.3±0.7 respectively).

Results: We found significantly increased frequency of heterozygous and homozygous polymorphic BclI and A3669G allele in patients with autoimmune thyroid disorders in comparison with healthy control subjects, while there was no difference in other GR gene polymorphisms. There was no difference in BclI and A3669G frequency between patients with Hashimoto thyroiditis and Graves hyperthyroidism.

Conclusion: Increased frequency of the GR gene BclI and A3669G polymophisms suggests possible role of this polymorphic alleles in pathogenesis of autoimmune thyroid disease. Concerning the fact that presence of BclI polymorphism is associated with glucocorticoid hypersensitivity, and presence of A3669G results in relative GC insensitivity seen in a variety of immunerelated diseases, their precise role in AITD has to be defined in the future.

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