Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients
<b>Background/Objectives</b>: 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. <b>Methods</b>: This was a prosp...
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| author | Sara Labay-Tejado Virginia Fortuna Néstor Ventura-Abreu Mar Hernaez Valeria Opazo-Toro Alba Garcia-Humanes Mercè Brunet Elena Milla |
| author_facet | Sara Labay-Tejado Virginia Fortuna Néstor Ventura-Abreu Mar Hernaez Valeria Opazo-Toro Alba Garcia-Humanes Mercè Brunet Elena Milla |
| author_sort | Sara Labay-Tejado |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: 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. <b>Methods</b>: 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 (<i>PTGFR</i>) (rs3766355, rs3753380); beta-2-adrenergic receptor (<i>ADRB2</i>) (rs1042714); and cytochrome P450 2D6 (<i>CYP2D6</i>) (<i>*2</i> rs16947; <i>*35</i> rs769258; <i>*4</i> rs3892097; <i>*9</i> rs5030656, and <i>*41</i> 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 <i>CYP2D6</i> copy number variation were also evaluated. <b>Results</b>: In total, 112 eyes were treated with PGAs (58.0%), 59 with BBs (30.6%), and 22 with PDs (11.4%). For <i>PTGFR</i> (rs3753380), statistically significant differences were observed in vIOP in the PGA group (<i>p</i> = 0.032). Differences were also observed for <i>ADRB2</i> (rs1042714) in MD (<i>p</i> < 0.001) and vIOP (<i>p</i> = 0.017). For <i>CYP2D6</i>, ultrarapid metabolizers exhibited higher tIOP (<i>p</i> = 0.010) and lower vIOP (<i>p</i> = 0.046) compared to the intermediate and poor metabolizers of the BB group. Additionally, systemic treatment metabolized by <i>CYP2D6</i> showed a significant influence on vIOP (<i>p</i> = 0.019) in this group. <b>Conclusions</b>: 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. |
| format | Article |
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| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-ee7682a8fc2e4a72a3d6cddd92b0d9922025-08-20T01:48:57ZengMDPI AGPharmaceutics1999-49232025-03-0117332510.3390/pharmaceutics17030325Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma PatientsSara Labay-Tejado0Virginia Fortuna1Néstor Ventura-Abreu2Mar Hernaez3Valeria Opazo-Toro4Alba Garcia-Humanes5Mercè Brunet6Elena Milla7Department of Ophthalmology (ICOF), Hospital Clínic de Barcelona, Universitat de Barcelona, Carrer de Sabino Arana 1, 08028 Barcelona, SpainDepartment of Biochemistry and Molecular Genetics (CDB), Hospital Clínic de Barcelona, Carrer de Villaroel 170, 08036 Barcelona, SpainDepartment of Glaucoma (ICOF), Hospital Clínic de Barcelona, Universitat de Barcelona, Carrer de Sabino Arana 1, 08028 Barcelona, SpainDepartment of Biochemistry and Molecular Genetics (CDB), Hospital Clínic de Barcelona, Carrer de Villaroel 170, 08036 Barcelona, SpainSkövde’s Ophthalmology Department, Skaraborg’s Hospital, Lövänsvägen, 549 49 Skövde, SwedenDepartment of Biochemistry and Molecular Genetics (CDB), Hospital Clínic de Barcelona, Carrer de Villaroel 170, 08036 Barcelona, SpainDepartment of Biochemistry and Molecular Genetics (CDB), Hospital Clínic de Barcelona, Carrer de Villaroel 170, 08036 Barcelona, SpainDepartment of Glaucoma (ICOF), Hospital Clínic de Barcelona, Universitat de Barcelona, Carrer de Sabino Arana 1, 08028 Barcelona, Spain<b>Background/Objectives</b>: 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. <b>Methods</b>: 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 (<i>PTGFR</i>) (rs3766355, rs3753380); beta-2-adrenergic receptor (<i>ADRB2</i>) (rs1042714); and cytochrome P450 2D6 (<i>CYP2D6</i>) (<i>*2</i> rs16947; <i>*35</i> rs769258; <i>*4</i> rs3892097; <i>*9</i> rs5030656, and <i>*41</i> 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 <i>CYP2D6</i> copy number variation were also evaluated. <b>Results</b>: In total, 112 eyes were treated with PGAs (58.0%), 59 with BBs (30.6%), and 22 with PDs (11.4%). For <i>PTGFR</i> (rs3753380), statistically significant differences were observed in vIOP in the PGA group (<i>p</i> = 0.032). Differences were also observed for <i>ADRB2</i> (rs1042714) in MD (<i>p</i> < 0.001) and vIOP (<i>p</i> = 0.017). For <i>CYP2D6</i>, ultrarapid metabolizers exhibited higher tIOP (<i>p</i> = 0.010) and lower vIOP (<i>p</i> = 0.046) compared to the intermediate and poor metabolizers of the BB group. Additionally, systemic treatment metabolized by <i>CYP2D6</i> showed a significant influence on vIOP (<i>p</i> = 0.019) in this group. <b>Conclusions</b>: 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.https://www.mdpi.com/1999-4923/17/3/325glaucomaintraocular pressurevisual fieldpharmacogeneticspersonalized treatmentsingle-nucleotide polymorphism |
| spellingShingle | Sara Labay-Tejado Virginia Fortuna Néstor Ventura-Abreu Mar Hernaez Valeria Opazo-Toro Alba Garcia-Humanes Mercè Brunet Elena Milla Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients Pharmaceutics glaucoma intraocular pressure visual field pharmacogenetics personalized treatment single-nucleotide polymorphism |
| title | Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients |
| title_full | Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients |
| title_fullStr | Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients |
| title_full_unstemmed | Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients |
| title_short | Pharmacogenetic Influences on Individual Responses to Ocular Hypotensive Agents in Glaucoma Patients |
| title_sort | pharmacogenetic influences on individual responses to ocular hypotensive agents in glaucoma patients |
| topic | glaucoma intraocular pressure visual field pharmacogenetics personalized treatment single-nucleotide polymorphism |
| url | https://www.mdpi.com/1999-4923/17/3/325 |
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