Abstract
Purpose::
Off-label injection of intravitreal triamcinolone acetonide (IVTA) is a common treatment for various macular diseases. A major complication of IVTA is increased intraocular pressure (IOP) and steroid-induced glaucoma. Presently, it is not possible to predict which patients will develop complications, although some reports have suggested that genetic factors may be predisposing. In this study, we sought a pharmacogenomic relationship between IVTA-induced IOP elevation and polymorphisms in the glucocorticoid receptor gene.
Methods::
Fifty-two patients treated with IVTA met all entry criteria for this study. The major clinical data points were baseline IOP and maximum IOP recorded during the 3 months following injection. DNA analysis was performed for 6 well known polymorphisms of the glucocorticoid receptor gene (GluArg22/23GluLys, Asn363Ser, IVS2+646C>G, IVS3-4G>C, IVS4-16G>T, and Asn766Asn).
Results::
The polymorphisms GluArg22/23GluLys, Asn363Ser, and IVS3-4G>C showed little variation within this sample and were excluded from more detailed analysis. The polymorphisms IVS2+646C>G, IVS4-16G>T, and Asn766Asn met Hardy-Weinberg equilibrium. No polymorphism was individually associated with IOP response via regression analysis. Six different haplotypes studied via regression analysis were not associated with IOP response.
Conclusions::
In this small pilot study, we did not find a pharmacogenomic relationship between genetic polymorphisms in the glucocorticoid receptor and IVTA-induced IOP elevation. At this time, we are continuing to recruit patients in order to do a complete steroid pathway candidate gene analysis, and ultimately a whole genome screen.
Keywords: corticosteroids • age-related macular degeneration • gene screening