PTGFR and SLCO2A1 Gene Polymorphisms Determine Intraocular Pressure Response to Latanoprost in Han Chinese Patients with Glaucoma

Abstract

An association was found between single nucleotide polymorphisms of the PTGFR and SLCO2A1 genes and the response to latanoprost in Han Chinese patients with glaucoma. These SNPs may be important determinants of differential response to latanoprost.

Stanniocalcin-1 (STC-1), a downstream effector molecule in latanoprost signaling, acts independent of the FP receptor for intraocular pressure reduction

“…PGF2α analogues such as latanoprost are generally well-tolerated and effective in reducing elevated IOP in many patients with ocular hypertension and glaucoma. However, their use is limited in some patient populations due to side effects or lack of treatment response [6][7][8][9][10][11][12][13][14][15][16]. Because of their restricted use, development of new therapeutics that can treat these patient populations would be welcomed.…”

“…molecule downstream of PGF2α also has the potential to have a reduced side-effect profile for patients that have experienced conjunctival hyperemia, ocular surface irritation, hyper-pigmentation of the iris and periocular skin, orbital fat atrophy, hypertrichosis, [13] intraocular inflammation, [14,15] reactivation of herpes simplex keratitis, or macular edema [16] with traditional PGF2α analogues. It remains to be seen whether the 20% of patients with reduced or no response to topical PGF2α that has been associated with SNPs in the FP receptor [7][8][9][10][11][12] may have benefit from topical STC-1. Additionally, it has been proposed that the poor IOPlowering with latanoprost treatment observed in patients with Axenfeld-Rieger malformation is due to abnormal signaling in the FOXC1-FP receptor signaling axis [32,33].…”

“…Up to 20% of patients with ocular hypertension or multiple types of glaucoma including low tension, primary open angle, exfoliative, or pigment dispersion have a reduced or absent response to PGF2α analogues [4][5][6]. Variability in PGF2α analogue response has been associated with single nucleotide polymorphisms (SNPs) in the FP receptor [7][8][9][10][11][12].…”

Expression, activity and pharmacokinetic impact of ocular transporters

“…Carriers of a genetic variant of MRP4 (rs11568658) had significantly lower intraocular pressure after latanoprost treatment, indicating that MRP4 efflux affects the absorption of latanoprost [96]. Similarly, an OATP2A1 genetic variant (rs4241366) was found to have some correlation to the intraocular pressure response after topically applied latanoprost in glaucoma patients [97]. Additionally, a MDR1 variant (3435c>T, rs1045642) was recently associated to the enhanced intraocular pressure response of latanoprost [98].…”

“…Additionally, a MDR1 variant (3435c>T, rs1045642) was recently associated to the enhanced intraocular pressure response of latanoprost [98]. Notably, several other studied variants of MRP4, MDR1 and OATP2A1 showed no impact on intraocular pressure response after latanoprost or other prostaglandin analog treatment [97,99]. OATP2A1 and MRP4 are both found at the corneal epithelium (Table 1), but MDR1 has not been detected.…”