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

Gao, Lichen; Wang, Di; Liu, Fang-qun; Huang, Zhengyu; Huang, Hongyang; Wang, Guihua; Chen, Xi; Shi, Qun-Zhi; Ling, Hong; Wu, Liping; Tang, Jie

doi:10.1007/s00228-014-1769-8

Cited by 18 publications

(22 citation statements)

References 23 publications

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“…The effect of polymorphisms on the response to latanoprost that is used as a treatment for glaucoma has been studied recently. Carriers of a genetic variant of MRP4 (rs11568658) had significantly lower intraocular pressure after latanoprost treatment, indicating that MRP4 efflux affects the absorption of latanoprost [96]. Similarly, an OATP2A1 genetic variant (rs4241366) was found to have some correlation to the intraocular pressure response after topically applied latanoprost in glaucoma patients [97].…”

Section: Accepted Manuscript 6 Pharmacogenetics In Omentioning

confidence: 95%

Expression, activity and pharmacokinetic impact of ocular transporters

Vellonen

Hellinen

Mannermaa

et al. 2018

Advanced Drug Delivery Reviews

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The eye is protected by several tissues that limit the permeability and entry of potentially harmful substances, but also hamper the delivery of drugs in the treatment of ocular diseases. Active transport across the ocular barriers may affect drug distribution, but the impact of drug transporters on ocular drug delivery is not well known. We have collected and critically reviewed the literature for ocular expression and activity of known drug transporters. The review concentrates on drug transporters that have been functionally characterized in ocular tissues or primary cells and on transporters for which there is available expression data at the protein level. Species differences are highlighted, since these may explain observed inconsistencies in the influence of specific transporters on drug disposition. There is variable evidence about the pharmacokinetic role of transporters in ocular tissues. The strongest evidence for the role of active transport is available for the blood-retinal barrier. We explored the role of active transport in the cornea and blood retinal barrier with pharmacokinetic simulations. The simulations show that the active transport is important only in the case of specific parameter combinations.

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Section: Accepted Manuscript 6 Pharmacogenetics In Omentioning

confidence: 95%

Expression, activity and pharmacokinetic impact of ocular transporters

Vellonen

Hellinen

Mannermaa

et al. 2018

Advanced Drug Delivery Reviews

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“…Moreover, it was shown in the Japanese childhood acute lymphoblastic leukemia (ALL) population that the homozygous variant allele in any of the ABCC4 2269G.A, 912C.A, and 559G.T variants was in correlation with reduced 6-MP dose (Tanaka et al, 2014). More recently, Gao et al (2015) reported that 559G.T was significantly associated with decreased intraocular pressure in response to latanoprost. However, whether these SNPs reduce protein location or expression and impair the binding ability of MRP4 substrates and the mechanism responsible need further investigation.…”

Section: Pharmacogenomics Of Mrp4mentioning

confidence: 99%

The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

Wen

Luo

Huang

et al. 2015

J Pharmacol Exp Ther

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Multidrug-resistant protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is distributed in a variety of tissues and a number of cancers. As a drug transporter, MRP4 is responsible for the pharmacokinetics and pharmacodynamics of numerous drugs, especially antiviral drugs, antitumor drugs, and diuretics. In this regard, the functional role of MRP4 is affected by a number of factors, such as genetic mutations; tissue-specific transcriptional regulations; post-transcriptional regulations, including miRNAs and membrane internalization; and substrate competition. Unlike other C family members, MRP4 is in a pivotal position to transport cellular signaling molecules, through which it is tightly connected to the living activity and physiologic processes of cells and bodies. In the context of several cancers in which MRP4 is overexpressed, MRP4 inhibition shows striking effects against cancer progression and drug resistance. In this review, we describe the role of MRP4 more specifically in both healthy conditions and disease states, with an emphasis on its potential as a drug target.

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“…Meanwhile, the patient's gender correlated with the IOP reduction on day 7, but not on day 30. Sakurai et al 7 and Gao et al 8 found that baseline IOP did not correlate with %ΔIOP. These findings suggest that the key factors related to IOP reduction may be more complicated in patients with high baseline IOP than in patients with low baseline IOP.…”

Section: Discussionmentioning

confidence: 97%

“…However, previous studies showed inconsistent findings between the SNPs of PTGER and the response to latanoprost. 6,8,9 Racial heterogeneity (differences in MAF) may be an important factor responsible for the inconsistency between studies. 5,19 For example, the MAF of rs12093097 (0.114) in this study was lower than that of the NCBI SNP database (0.2376).…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Two SNPs (rs3753380 and rs3766355) of the prostaglandin F 2α receptor (PTGFR) gene were found to correlate with the response to short-term latanoprost treatment in normal volunteers, 6 and rs12093097 was found to correlate with the response to latanoprost in patients with primary open angle glaucoma (POAG) and ocular hypertension (OH). 7 Similarly, Gao et al 8 also found that rs3753380 and rs3766355 in PTGFR gene may be important determinants of variability in response to latanoprost. However, McCarty et al 9 found no association between SNPs in the PTGFR gene or solute carrier organic anion transporter family 2A1 (SLCO2A1) gene and response to prostaglandin analogs.…”

Section: Introductionmentioning

confidence: 94%

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