The variant N363S of glucocorticoid receptor in steroid-induced ocular hypertension in Hungarian patients treated with photorefractive keratectomy.
OBJECTIVE
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.
Szabó
Viktória
V
Department of Ophthalmology, KFKI Research Institute for Particle and Nuclear Physics of the Hungarian Academy of Sciences, Budapest, Hungary. szabo_viktoria@hotmail.com
Borgulya
Gábor
G
Filkorn
Tamás
T
Majnik
Judit
J
Bányász
Ilona
I
Nagy
Zoltán Zsolt
ZZ
D000328:Adult; D048988:Corneal Surgery, Laser; D005260:Female; D005469:Fluorometholone / Q000009:adverse effects / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006579:Heterozygote; D006801:Humans; D006814:Hungary; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000139:chemically induced* / Q000235:genetics*; D011182:Postoperative Care; D011239:Prednisolone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D019233:Retreatment; D013256:Steroids / Q000009:adverse effects*
D005938:Glucocorticoids; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D013256:Steroids; C009935:prednisolone acetate; D011239:Prednisolone; D005469:Fluorometholone