Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients

The purpose of this study is to evaluate the association between variants in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin F (2 alpha) receptor (PTGFR), and multidrug resistance protein 4 (MRP4) genes and intraocular pressure (IOP) response to latanoprost in Chinese patients with primary open-angle glaucoma (POAG). The IOP response to latanoprost was evaluated by percent IOP reduction (%Delta IOP) in the treated eye with the formula %Delta IOP = (Baseline IOP values -aEuro parts per thousand IOP values posttreatment) / Baseline IOP values x 100 %. Polymorphisms in PTGS1 (rs3842787 and rs10306114), PTGFR (rs3753380 and rs3766355), and MRP4 (rs11568658 and rs11568668) genes were detected by direct DNA sequencing. The differences among %Delta IOP of genotypes or haplotypes were obtained by use of the Mann-Whitney U test. Association analyses were performed by multiple linear regression analysis. Latanoprost were prescribed to 63 subjects, 60 of which met the inclusion/exclusion criteria for the current study. Notably, the %Delta IOP in the rs11568658 GT heterozygous genotype was 10.4 %Delta IOP lower than that of GG homozygous wild-type on day 7 (15.7 +/- 2.52 vs. 26.1 +/- 2.88, P = 0.003), and the corresponding results in the rs10306114 AG heterozygous genotype and AT haplotype constructed by rs3753380 and rs3766355 on day 7 were 7.2 and 10.3 %Delta IOP (P < 0.05). Interestingly, similar results were also observed on day 30 (P = 0.008, P = 0.006, and P = 0.002, respectively). Multiple regression analysis showed that heterozygous genotypes of rs10306114, rs11568658, and carrier of AT haplotype were significantly correlated with the lower %Delta IOP. On day 30, the above variations explained 9.9, 10.7, and 17.7 % of the total variability of %Delta IOP in the Chinese POAG patients, respectively. rs10306114, rs3753380, rs3766355, and rs11568658 single-nucleotide polymorphisms (SNPs) correlate with a response to latanoprost treatment in patients with POAG. These SNPs may be important determinants of variability in response to latanoprost.