Polymorphisms of the glucocorticoid receptor gene in Graves ophthalmopathy.
OBJECTIVE
Glucocorticoids have an important role in the regulation of the immune system, and alterations in glucocorticoid signaling may have an impact on the pathophysiology of autoimmune and inflammatory disorders. Because polymorphisms of the glucocorticoid receptor (GR) gene, including the N363S, ER22/23EK, A3669G and BclI variants were found to influence glucocorticoid signalling, we examined whether these polymorphisms could be associated with the development or clinical manifestations of Graves ophthalmopathy (GO).


METHODS
The carrier and allelic frequencies of the N363S, ER22/23EK, A3669G, and BclI polymorphisms of the GR were determined in 95 Hungarian outpatients with GO and 160 healthy controls.


RESULTS
No significant changes were found in carrier frequencies of the four polymorphisms between GO patients and healthy controls. However, when GO patients were divided into two subgroups (American Thyroid Association Committee, ATA I-II vs ATA III or greater), the frequency of the polymorphic BclI allele was significantly higher in patients with ATA I-II compared with those with ATA III or more (p = 0.009).


CONCLUSIONS
The significant association between the frequency of the polymorphic BclI allele and ATA stage distribution suggests that this polymorphism of the GR gene may affect clinical manifestations of GO, presumably due to an increased signaling of endogenous glucocorticoids.
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D049970:Graves Ophthalmopathy / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012720:Severity of Illness Index
D011965:Receptors, Glucocorticoid