PTGFR gene: a potential candidate gene for glaucoma and pharmacodynamic gene in Malaysian population

Liza-Sharmini AT^1,2>Waseem N2, Rusli I³, Zilfalil BA⁴, Viswanathan A², Foster PJ²

Purpose:
To determine the association of PTGFR between glaucoma patients and healthy controls and to determine the role of PTGFR in responsiveness to topical latanoprost

Methods:
A prospective cohort study was conducted on 90 OAG patients; 45.6% of them were treated with latanoprost as monotherapy and 54.4% were on adjunctive therapy. They were followed up for 12 months with IOP measurement taken 3 monthly. Ninety age-matched of healthy controls were also recruited. Venesection was done and 3ml of blood was obtained for genotype. DNA extraction was done using commercially available kit. PCR was conducted and direct sequencing of the whole gene including the 3000bp upstream from exon 1 region was conducted to identify the sequence variants of PTGFR. Two microsatellite instability was also detected in intron 3.

Results:
Topical latanoprost 0.005% provided pressure lowering effect of 7.08SD4.17 (mean percentage of 27.05SD19.28) and without significant different between monotherapy and adjunctive therapy (p=0.774). There was significant reduction of IOP from the baseline based on repeated measures ANOVA. rs4650581 (p=0.005), rs34012237 (p=0.045) and rs3766335 (p=0.005) found in introns 3 of PTGFR gene was significantly associated with pressure lowering effect of latanoprost. Homozygous mutant was found to associate with poor pressure lowering effect. There was significant association of PTGFR gene with susceptibility of glaucoma with odd ratio of 5.2 of rs1116504 to develop glaucoma, while homozygous wild rs1116505 has protective effect against glaucoma.

Conclusion:
PTGFR is potential candidate gene for OAG in Malaysian population. PTGFR is a strong predictor to determine the response to latanoprost.