Association between Genetic Polymorphisms of the Prostaglandin F_2α Receptor Gene and Response to Latanoprost

Purpose

To evaluate the relationship between polymorphisms of the prostaglandin F_2α receptor (FP receptor) gene and the effectiveness of topical latanoprost treatment in normal volunteers.

Design

Prospective nonrandomized trial.

Participants

One hundred normal volunteers were recruited into the study.

Methods

Baseline intraocular pressures (IOPs) of both eyes of 100 normal subjects were measured at 3 time points. Latanoprost (0.005%) was applied to one eye once daily for 7 days. Diurnal IOP was measured again on day 7. Response to latanoprost was evaluated by percent IOP reduction in the treated eye minus IOP fluctuations of the nontreated eye. We classified subjects by the mean diurnal percent IOP reduction (%ΔIOP) into 3 groups: low responders (%ΔIOP<10), medium responders (10≤%ΔIOP<25), and high responders (%ΔIOP≥25). Single-nucleotide polymorphisms (SNPs) in the FP receptor gene were searched, and the genotype was determined mainly by direct DNA sequencing. A promoter assay with a reporter luciferase gene was also performed.

Main Outcome Measures

Mean diurnal percent IOP reduction and genotyping of SNPs in the FP receptor gene.

Results

Ten SNPs were identified in this study. One, rs3753380, was located in the promoter region of the FP receptor gene and was significantly correlated with %ΔIOP (CC, 20.3%±1.5% [mean ± standard error]; CT + TT, 15.6%±1.2%; P = 0.0316). Mean diurnal percent IOP reduction was not associated with the other SNPs. When the category classified by %ΔIOP was analyzed, not only rs3753380 but also rs3766355, an SNP in intron 1, were associated with the degree of response to latanoprost. The promoter assay revealed that the C allele of rs3766355 and T allele of rs3753380 were found in constructs with lower transcriptional activity of the FP receptor gene.

Conclusions

rs3753380 and rs3766355, SNPs in the promoter and intron 1 regions of the FP receptor gene, correlate with a response to short-term latanoprost treatment in normal volunteers. The genotype of these SNPs may be an important determinant of variability in response to latanoprost.