The variant N363S of glucocorticoid receptor in steroid-inducedocular hypertension in Hungarian patients treated with photorefractivekeratectomy

[摘要] Purpose: Variation in sensitivity to glucocorticoids observed inhealthy population is influenced by genetic polymorphisms of theglucocorticoid receptor gene (NR3C1). N363S, ER22/23EK, and Bcl Ihave been previously described as glucocorticoid-sensitivity modulatingpolymorphisms. We investigated whether these variants may contribute tosteroid-induced ocular hypertension and if they play a role asprotective or risk factors during exogenous glucocorticoidadministration.Methods: We examined 102 patients who underwent photorefractivekeratectomy and received topical steroids (either fluorometholone 0.1%or prednisolone acetate 0.5% alone or combined) as part of postoperativetherapy. The choice of steroid depended on course of wound healing andregression. Variations in intraocular pressure (IOP) levels in responseto steroid therapy were observed. To genotype DNA, allele-specific PCRamplification was applied for the N363S polymorphism, and PCR-basedrestriction fragment length polymorphism analysis was performed toexamine the Bcl I and the ER22/23EK polymorphisms. We separatelyanalyzed data from three groups of patients: those who receivedfluorometholone only; those who were initially given fluorometholonethen later switched to prednisolone acetate; and those who receivedprednisolone acetate only. Covariance analysis with forward stepwisevariable selection was carried out.Results: In cases where prednisolone acetate was administered, wefound a significant correlation between N363S heterozygosity andsteroid-induced ocular hypertension. ER22/23EK and Bcl I polymorphismsdo not have a major influence on the risk of developing steroid-inducedocular hypertension.Conclusions: Genotyping of high risk steroid responders may allow anindividual therapy to avoid steroid-induced ocular hypertension. TheN363S polymorphism may have a clinical significance in the future.

[学科分类] 生物化学/生物物理