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Abstract #17437 Published in IGR 9-2
The variant N363S of glucocorticoid receptor in steroid-induced ocular hypertension in Hungarian patients treated with photorefractive keratectomy
Szabo V; Borgulya G; Filkorn T; Majnik J; Banyasz I; Nagy ZZMolecular Vision 2007; 13: 659-666
PURPOSE: Variation in sensitivity to glucocorticoids observed in healthy population is influenced by genetic polymorphisms of the glucocorticoid receptor gene (NR3C1). N363S, ER22/23EK, and Bcl I have been previously described as glucocorticoid-sensitivity modulating polymorphisms. We investigated whether these variants may contribute to steroid-induced ocular hypertension and if they play a role as protective or risk factors during exogenous glucocorticoid administration. METHODS: We examined 102 patients who underwent photorefractive keratectomy and received topical steroids (either fluorometholone 0.1% or prednisolone acetate 0.5% alone or combined) as part of postoperative therapy. The choice of steroid depended on course of wound healing and regression. Variations in intraocular pressure (IOP) levels in response to steroid therapy were observed. To genotype DNA, allele-specific PCR amplification was applied for the N363S polymorphism, and PCR-based restriction fragment length polymorphism analysis was performed to examine the Bcl I and the ER22/23EK polymorphisms. We separately analyzed data from three groups of patients: those who received fluorometholone only; those who were initially given fluorometholone then later switched to prednisolone acetate; and those who received prednisolone acetate only. Covariance analysis with forward stepwise variable selection was carried out. RESULTS: In cases where prednisolone acetate was administered, we found a significant correlation between N363S heterozygosity and steroid-induced ocular hypertension. ER22/23EK and Bcl I polymorphisms do not have a major influence on the risk of developing steroid-induced ocular hypertension. CONCLUSIONS: Genotyping of high risk steroid responders may allow an individual therapy to avoid steroid-induced ocular hypertension. The N363S polymorphism may have a clinical significance in the future.
Dr. V. Szabo, Department of Ophthalmology, Tomo 25-29, Budapest 1083, Hungary. Zabo_viktoria@hotmail.com
Classification:
9.4.1 Steroid-induced glaucoma (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
8.4 Refractive surgical procedures (Part of: 8 Refractive errors in relation to glaucoma)
