Glucocorticoid Receptor Binding Sites Are Enriched For Genetic Associations With Intraocular Pressure Variation

Purpose: Glucocorticoids (GC) are a class of steroid hormones with strong anti-inflammatory effects used to treat various conditions, including ocular disorders. GCs regulate gene expression by binding to glucocorticoid receptors (GR) in the cytoplasm, which in turn translocate to the nucleus and either bind directly to glucocorticoid response elements (GREs) throughout the genome or indirectly via tethering to other transcription factors. GCs elevate intraocular pressure (IOP) in a large proportion of patients, which can lead to optic nerve damage and vision loss. There is long-standing evidence that genetic factors influence the development of GC-induced ocular hypertension; however, the genetic basis remains unknown. Here we test the hypothesis that common variants in GR binding sites (GBS) affect IOP levels.Methods: We assessed whether common variants (minor allele frequency, MAF> 1%) that fall in direct …