Glucocorticoid receptor polymorphisms and intraocular pressure response to intravitreal triamcinolone acetonide.
BACKGROUND
Elevation of intraocular pressure (IOP) following injection of intravitreal triamcinolone acetonide (IVTA) is an important clinical problem. The etiology of the steroid response is poorly understood, although a genetic determinant has long been suspected. We performed a pharmacogenomic association study with glucocorticoid receptor polymorphisms.


METHODS
Fifty-two patients (56 eyes) who underwent treatment with IVTA for various retinal diseases were genotyped for six well-studied glucocorticoid receptor polymorphisms (ER22/23EK, N363S, BclI, N766N, and single nucleotide polymorphisms (SNPs) within introns 3 and 4).


RESULTS
Three polymorphisms (ER22/23EK, N363S, and the intron 3 SNP) were essentially nonpolymorphic within this population sample and excluded from further analysis. The remaining three polymorphisms (BclI, N766N, and within intron 4) passed the Hardy-Weinberg Equilibrium test, indicating good genotyping quality and normal population distribution of allelic frequency. No statistically significant correlations were found between these three polymorphisms and magnitude of IOP elevation following IVTA, using single point association and haplotype analyses.


CONCLUSIONS
In this small, pilot study, we found no statistically significant relationship between glucocorticoid receptor polymorphisms and IOP elevation following IVTA. The precise etiology of the steroid response remains obscure. To our knowledge, this is the first published pharmacogenomic study of this common clinical entity.
Gerzenstein
Sabrina M
SM
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
Pletcher
Mathew T
MT
Cervino
Alessandra C L
AC
Tsinoremas
Nicholas F
NF
Young
Brandon
B
Puliafito
Carmen A
CA
Fini
M Elizabeth
ME
Schwartz
Stephen G
SG
D000368:Aged; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use*; D006239:Haplotypes; D006801:Humans; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D010597:Pharmacogenetics; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012164:Retinal Diseases / Q000188:drug therapy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014222:Triamcinolone Acetonide / Q000627:therapeutic use*; D014822:Vitreous Body
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014222:Triamcinolone Acetonide