title: Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients.
abstract: OBJECTIVE
  The purpose of this study is to evaluate the association between variants in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin F (2α) 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).
  
  
  METHODS
  The IOP response to latanoprost was evaluated by percent IOP reduction (%ΔIOP) in the treated eye with the formula %ΔIOP = (Baseline IOP values - IOP values posttreatment) / Baseline IOP values × 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 %ΔIOP of genotypes or haplotypes were obtained by use of the Mann-Whitney U test. Association analyses were performed by multiple linear regression analysis.
  
  
  RESULTS
  Latanoprost were prescribed to 63 subjects, 60 of which met the inclusion/exclusion criteria for the current study. Notably, the %ΔIOP in the rs11568658 GT heterozygous genotype was 10.4 %ΔIOP 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 %ΔIOP (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 %ΔIOP. On day 30, the above variations explained 9.9, 10.7, and 17.7 % of the total variability of %ΔIOP in the Chinese POAG patients, respectively.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Department of Oncology, Cancer Institute, Changsha Central Hospital, Changsha, Hunan, China, gonedog1224@hotmail.com.
authors.forename: Li-chen
authors.initials: LC
authors.lastname: Gao
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Fang-qun
authors.initials: FQ
authors.lastname: Liu
authors.forename: Zheng-yu
authors.initials: ZY
authors.lastname: Huang
authors.forename: Hong-guang
authors.initials: HG
authors.lastname: Huang
authors.forename: Gui-hua
authors.initials: GH
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Qun-zhi
authors.initials: QZ
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Hong
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044466:Asian People / Q000235:genetics*; D051545:Cyclooxygenase 1 / Q000235:genetics; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000235:genetics
chemical_list: D000959:Antihypertensive Agents; D051545:Cyclooxygenase 1; D000077338:Latanoprost; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C073492:ABCC4 protein, human; C034671:prostaglandin F2alpha receptor; C496511:PTGS1 protein, human