Association between genetic polymorphisms of the prostaglandin F2alpha receptor gene and response to latanoprost.
OBJECTIVE
To evaluate the relationship between polymorphisms of the prostaglandin F(2alpha) receptor (FP receptor) gene and the effectiveness of topical latanoprost treatment in normal volunteers.


METHODS
Prospective nonrandomized trial.


METHODS
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 (%DeltaIOP) into 3 groups: low responders (%DeltaIOP<10), medium responders (10< or =%DeltaIOP<25), and high responders (%DeltaIOP> or =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.


METHODS
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 %DeltaIOP (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 %DeltaIOP 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.
Sakurai
Mayumi
M
Department of Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Higashide
Tomomi
T
Takahashi
Mami
M
Sugiyama
Kazuhisa
K
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002940:Circadian Rhythm; D005260:Female; D005838:Genotype; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D007438:Introns / Q000235:genetics; D000077338:Latanoprost; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use*; D011982:Receptors, Prostaglandin / Q000235:genetics*; D014065:Tonometry, Ocular
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D000077338:Latanoprost