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药物遗传学对青光眼患者眼压降低药物个体反应的影响。

Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients.

作者信息

Labay-Tejado Sara, Fortuna Virginia, Ventura-Abreu Néstor, Hernaez Mar, Opazo-Toro Valeria, Garcia-Humanes Alba, Brunet Mercè, Milla Elena

机构信息

Department of Ophthalmology (ICOF), Hospital Clínic de Barcelona, Universitat de Barcelona, Carrer de Sabino Arana 1, 08028 Barcelona, Spain.

Department of Biochemistry and Molecular Genetics (CDB), Hospital Clínic de Barcelona, Carrer de Villaroel 170, 08036 Barcelona, Spain.

出版信息

Pharmaceutics. 2025 Mar 2;17(3):325. doi: 10.3390/pharmaceutics17030325.

DOI:10.3390/pharmaceutics17030325
PMID:40142989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11944811/
Abstract

: To analyze the genotype that predicts the phenotypic characteristics of a cohort of patients with glaucoma and ocular hypertension (OHT) and explore their influence on the response to ocular hypotensive treatment. : This was a prospective study that included 193 eyes of 109 patients with glaucoma or OHT under monotherapy with beta-blockers, prostaglandin, or prostamide analogues (BBs, PGAs, PDs). Eight single-nucleotide polymorphisms were genotyped using real-time PCR assays: prostaglandin-F2α receptor () (rs3766355, rs3753380); beta-2-adrenergic receptor () (rs1042714); and cytochrome P450 2D6 () ( rs16947; rs769258; rs3892097; rs5030656, and rs28371725). The main variables studied were baseline (bIOP), treated (tIOP), and rate of variation in intraocular pressure (vIOP), and mean deviation of the visual field (MD). The metabolizer phenotype and the copy number variation were also evaluated. : In total, 112 eyes were treated with PGAs (58.0%), 59 with BBs (30.6%), and 22 with PDs (11.4%). For (rs3753380), statistically significant differences were observed in vIOP in the PGA group ( = 0.032). Differences were also observed for (rs1042714) in MD ( < 0.001) and vIOP ( = 0.017). For , ultrarapid metabolizers exhibited higher tIOP ( = 0.010) and lower vIOP ( = 0.046) compared to the intermediate and poor metabolizers of the BB group. Additionally, systemic treatment metabolized by showed a significant influence on vIOP ( = 0.019) in this group. : These preliminary findings suggest the future potential of pharmacogenetic-based treatments in glaucoma to achieve personalized treatment for each patient, and thus optimal clinical management.

摘要

分析预测青光眼和高眼压症(OHT)患者队列表型特征的基因型,并探讨其对降眼压治疗反应的影响。:这是一项前瞻性研究,纳入了109例接受β受体阻滞剂、前列腺素或前列腺酰胺类似物(BBs、PGAs、PDs)单一疗法治疗的青光眼或OHT患者的193只眼睛。使用实时PCR检测对8个单核苷酸多态性进行基因分型:前列腺素-F2α受体()(rs3766355、rs3753380);β-2肾上腺素能受体()(rs1042714);以及细胞色素P450 2D6()(rs16947;rs769258;rs3892097;rs5030656和rs28371725)。研究的主要变量为基线眼压(bIOP)、治疗后眼压(tIOP)、眼压变化率(vIOP)和视野平均偏差(MD)。还评估了代谢酶表型和拷贝数变异。:总共112只眼睛接受了PGAs治疗(58.0%),59只接受了BBs治疗(30.6%),22只接受了PDs治疗(11.4%)。对于(rs3753380),在PGA组的vIOP中观察到统计学显著差异(=0.032)。在MD(<0.001)和vIOP(=0.017)中也观察到了(rs1042714)的差异。对于,与BB组的中间代谢型和慢代谢型相比,超快代谢型表现出更高的tIOP(=0.010)和更低的vIOP(=0.046)。此外,在该组中,由代谢的全身治疗对vIOP有显著影响(=0.019)。:这些初步发现表明基于药物遗传学的青光眼治疗在为每位患者实现个性化治疗从而实现最佳临床管理方面的未来潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/7d9d51f96396/pharmaceutics-17-00325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/2362784bb0ac/pharmaceutics-17-00325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/999fa6824c36/pharmaceutics-17-00325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/6b220d381329/pharmaceutics-17-00325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/0b7cb964ce39/pharmaceutics-17-00325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/ab5e6ec2d8c0/pharmaceutics-17-00325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/7d9d51f96396/pharmaceutics-17-00325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/2362784bb0ac/pharmaceutics-17-00325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/999fa6824c36/pharmaceutics-17-00325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/6b220d381329/pharmaceutics-17-00325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/0b7cb964ce39/pharmaceutics-17-00325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/ab5e6ec2d8c0/pharmaceutics-17-00325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b3/11944811/7d9d51f96396/pharmaceutics-17-00325-g006.jpg

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本文引用的文献

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Factors Affecting Glaucoma Medication Adherence and Interventions to Improve Adherence: A Narrative Review.影响青光眼药物依从性的因素及提高依从性的干预措施:一项叙述性综述
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Genotype and Phenotype Influence the Personal Response to Prostaglandin Analogues and Beta-Blockers in Spanish Glaucoma and Ocular Hypertension Patients.
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Clinical pharmacology and pharmacogenetics of prostaglandin analogues in glaucoma.前列腺素类似物在青光眼治疗中的临床药理学与药物遗传学
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Analysis of the Responsiveness of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in the Treatment of OAG/OHT Patients.拉坦前列素、曲伏前列素、比马前列素和他氟前列素治疗开角型青光眼/高眼压症患者的反应性分析。
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