Objective: To investigate whether three polymorphisms of the glucocorticoid receptor gene known to influence the sensitivity to glucocorticoids could be implicated in the pathomechanism of Graves orbitopathy.
Methods: Allelic frequencies of the ER22/23EK, Bcl l and N363S polymorphisms of the glucocorticoid receptor gene were investigated in 99 patients with Graves orbitopathy (mean age, 47.8±13.4 years) and in 175 healthy individuals (mean age 54.4±14.2 years). DNA was isolated from whole blood. Genotypes for the N363S and the Bcl l variants were determined by allele-specific polymerase chain reaction (PCR) and the ER22/23EK polymorphism was genotyped by PCR-RFLP analysis. The study was approved by local ethics committee, and written informed consent was obtained from all subjects.
Results: A significantly higher frequency of the ER22/23EK polymorphic allele was detected in patients with Graves orbitopathy compared to that found in healthy control subjects (allelic frequency 5.05% vs. 2.0%, P<0,05), whereas the allelic frequencies of the Bcl I and N363S polymorphisms were similar in the two groups.
Conclusion: In this study we found that the ER22/23EK polymorphic allele of the glucocorticoid receptor is significantly overrepresented in patients with Graves orbitopathy compared to healthy individuals. This polymorphism is known to be associated with a decreased sensitivity to glucocorticoids and, therefore, its high prevalence could increase the risk for the development of tissue-specific autoimmune inflammation underlying Graves orbitopathy.