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

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

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.

Conclusion

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.

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References

  1. (1998) The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. American journal of ophthalmology 126 (4): 498–505

  2. Quigley HA, Broman AT (2006) The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 90(3):262–267. doi:10.1136/bjo.2005.081224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Scherer WJ (2002) A retrospective review of non-responders to latanoprost. J Ocul Pharmacol Ther: Off J Assoc Ocul Pharmacol Ther 18(3):287–291. doi:10.1089/108076802760116205

    Article  CAS  Google Scholar 

  4. McCarty CA, Burmester JK, Mukesh BN, Patchett RB, Wilke RA (2008) Intraocular pressure response to topical beta-blockers associated with an ADRB2 single-nucleotide polymorphism. Arch Ophthalmol 126(7):959–963. doi:10.1001/archopht.126.7.959

    Article  CAS  PubMed  Google Scholar 

  5. Inagaki Y, Mashima Y, Fuse N, Funayama T, Ohtake Y, Yasuda N, Murakami A, Hotta Y, Fukuchi T, Tsubota K (2006) Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma. Mol Vis 12:673–680

    CAS  PubMed  Google Scholar 

  6. Sakurai M, Higashide T, Ohkubo S, Takeda H, Sugiyama K (2014) Association between genetic polymorphisms of the prostaglandin F2alpha receptor gene, and response to latanoprost in patients with glaucoma and ocular hypertension. Br J Ophthalmol 98(4):469–473. doi:10.1136/bjophthalmol-2013-304267

    Article  PubMed  Google Scholar 

  7. McCarty CA, Berg R, Patchett R, Wilke RA, Burmester JK (2012) Lack of association between polymorphisms in the prostaglandin F2alpha receptor and solute carrier organic anion transporter family 2A1 genes and intraocular pressure response to prostaglandin analogs. Ophthalmic Genet 33(2):74–76. doi:10.3109/13816810.2011.628357

    Article  CAS  PubMed  Google Scholar 

  8. Sakurai M, Higashide T, Takahashi M, Sugiyama K (2007) Association between genetic polymorphisms of the prostaglandin F2alpha receptor gene and response to latanoprost. Ophthalmology 114(6):1039–1045. doi:10.1016/j.ophtha.2007.03.025

    Article  PubMed  Google Scholar 

  9. Cryan LM, Fitzgerald DJ, O’Brien C (2009) Ocular prostaglandin production and morphology in mice lacking a single isoform of cyclooxygenase. Prostaglandins Leukot Essent Fat Acids 81(5–6):401–409. doi:10.1016/j.plefa.2009.08.001

    Article  CAS  Google Scholar 

  10. Neufeld AH, Hernandez MR, Gonzalez M, Geller A (1997) Cyclooxygenase-1 and cyclooxygenase-2 in the human optic nerve head. Exp Eye Res 65(6):739–745. doi:10.1006/exer.1997.0394

    Article  CAS  PubMed  Google Scholar 

  11. Motovska Z, Kvasnicka J, Hajkova J, Kala P, Simek S, Bobcikova P, Petr R, Bilkova D, Poloczek M, Miklik R, Fischerova M, Maly M, Widimsky P (2010) Platelet gene polymorphisms and risk of bleeding in patients undergoing elective coronary angiography: a genetic substudy of the PRAGUE-8 trial. Atherosclerosis 212(2):548–552. doi:10.1016/j.atherosclerosis.2010.07.006

    Article  CAS  PubMed  Google Scholar 

  12. Pattabiraman PP, Pecen PE, Rao PV (2013) MRP4-mediated regulation of intracellular cAMP and cGMP levels in trabecular meshwork cells and homeostasis of intraocular pressure. Invest Ophthalmol Vis Sci 54(3):1636–1649. doi:10.1167/iovs.12-11107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Zhu P, Zhu Q, Zhang Y, Ma X, Li Z, Li J, Chen J, Luo L, Ring HZ, Ring BZ, Su L (2013) ABCB1 variation and treatment response in AIDS patients: initial results of the Henan cohort. PLoS One 8(1):e55197. doi:10.1371/journal.pone.0055197

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Ulrich CM, Bigler J, Sibert J, Greene EA, Sparks R, Carlson CS, Potter JD (2002) Cyclooxygenase 1 (COX1) polymorphisms in African-American and Caucasian populations. Hum Mutat 20(5):409–410. doi:10.1002/humu.9080

    Article  PubMed  Google Scholar 

  15. Abla N, Chinn LW, Nakamura T, Liu L, Huang CC, Johns SJ, Kawamoto M, Stryke D, Taylor TR, Ferrin TE, Giacomini KM, Kroetz DL (2008) The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene. The J Pharmacol Exp Ther 325(3):859–868. doi:10.1124/jpet.108.136523

    Article  CAS  Google Scholar 

  16. Kawaguchi I, Higashide T, Ohkubo S, Kawaguchi C, Sugiyama K (2012) Comparison of efficacy of four prostaglandin analogues by bilateral treatment in healthy subjects. Jpn J Ophthalmol 56(4):346–353. doi:10.1007/s10384-012-0155-2

    Article  CAS  PubMed  Google Scholar 

  17. Wakabayashi Y, Higashide T, Sugiyama K (2011) Improved prediction of fellow-eye response in one-eye trials using multiple intraocular pressure measurements. Jpn J Ophthalmol 55(5):480–485. doi:10.1007/s10384-011-0054-y

    Article  PubMed  Google Scholar 

  18. Stjernschantz J, Selen G, Sjoquist B, Resul B (1995) Preclinical pharmacology of latanoprost, a phenyl-substituted PGF2 alpha analogue. Adv Prostaglandin Thromboxane Leukot Res 23:513–518

    CAS  PubMed  Google Scholar 

  19. Toris CB, Camras CB, Yablonski ME (1993) Effects of PhXA41, a new prostaglandin F2 alpha analog, on aqueous humor dynamics in human eyes. Ophthalmology 100(9):1297–1304

    Article  CAS  PubMed  Google Scholar 

  20. Ang A, Reddy MA, Shepstone L, Broadway DC (2004) Long term effect of latanoprost on intraocular pressure in normal tension glaucoma. Br J Ophthalmol 88(5):630–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Tamada Y, Taniguchi T, Murase H, Yamamoto T, Kitazawa Y (2001) Intraocular pressure-lowering efficacy of latanoprost in patients with normal-tension glaucoma or primary open-angle glaucoma. J Ocul Pharmacol Ther: Off J Assoc Ocul Pharmacol Ther 17(1):19–25. doi:10.1089/108076801750125612

    Article  CAS  Google Scholar 

  22. Maree AO, Curtin RJ, Chubb A, Dolan C, Cox D, O’Brien J, Crean P, Shields DC, Fitzgerald DJ (2005) Cyclooxygenase-1 haplotype modulates platelet response to aspirin. J Thromb Haemost: JTH 3(10):2340–2345. doi:10.1111/j.1538-7836.2005.01555.x

    Article  CAS  PubMed  Google Scholar 

  23. Lee CR, Bottone FG Jr, Krahn JM, Li L, Mohrenweiser HW, Cook ME, Petrovich RM, Bell DA, Eling TE, Zeldin DC (2007) Identification and functional characterization of polymorphisms in human cyclooxygenase-1 (PTGS1). Pharmacogenet Genomics 17(2):145–160. doi:10.1097/01.fpc.0000236340.87540.e3

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Kraft ME, Glaeser H, Mandery K, Konig J, Auge D, Fromm MF, Schlotzer-Schrehardt U, Welge-Lussen U, Kruse FE, Zolk O (2010) The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci 51(5):2504–2511. doi:10.1167/iovs.09-4290

    Article  PubMed  Google Scholar 

  25. Verschuren JJ, Boden H, Wessels JA, van der Hoeven BL, Trompet S, Heijmans BT, Putter H, Guchelaar HJ, Schalij MJ, Jukema JW (2013) Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction. Int J Cardiol 167(6):2882–2888. doi:10.1016/j.ijcard.2012.07.020

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to take this opportunity to thank Prof. Howard L. McLeod of the Institute of Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, North Carolina, for his important comments and Prof. Xiao-ping Chen, Prof. Dong-sheng Ouyang, and Dr. He-bin Xie for their excellent technical support on our paper.

This work was supported by the Grant from the Science and Technology Agency of Hunan Province (2014SK3272, 2014SS2033, and 2014TT2021) and the Grant from the Changsha Municipal Science and Technology Bureau (K13ZD075-33).

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Pharmacy, Department of Oncology, Cancer Institute, Changsha Central Hospital, Changsha, Hunan, China

    Li-chen Gao, Di Wang, Fang-qun Liu, Zheng-yu Huang, Hong-guang Huang, Gui-hua Wang, Xi Chen & Qun-zhi Shi

  2. Department of Obstetrics and Gynecology, Department of Anesthesiology, Hunan Province Geriatric Hospital, Changsha, Hunan, China

    Li Hong & Li-ping Wu

  3. Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China

    Jie Tang

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  1. Li-chen Gao
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Corresponding authors

Correspondence to Li-chen Gao or Fang-qun Liu.

Additional information

Gao LC and Wang D contributed equally to the work.

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Gao, Lc., Wang, D., Liu, Fq. et al. Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients. Eur J Clin Pharmacol 71, 43–50 (2015). https://doi.org/10.1007/s00228-014-1769-8

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