Genotype and Phenotype Influence the Personal Response to Prostaglandin Analogues and Beta-Blockers in Spanish Glaucoma and Ocular Hypertension Patients
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Published:2023-01-20
Issue:3
Volume:24
Page:2093
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Opazo-Toro Valeria1, Fortuna Virginia2, Jiménez Wladimiro34ORCID, Pazos López Marta5ORCID, Royo María Jesús Muniesa5, Ventura-Abreu Néstor6ORCID, Brunet Mercè34, Milla Elena45ORCID
Affiliation:
1. Glaucoma Unit, Instituto Oftalmologico Integral, C/María Auxiliadora 25, 08017 Barcelona, Spain 2. Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Service, Biomedical Diagnostic Center, Hospital Clinic Barcelona, University of Barcelona, 08007 Barcelona, Spain 3. Biochemistry and Molecular Genetics Service, Center for Biomedical Diagnosis, Hospital Clinic Barcelona, 08036 Barcelona, Spain 4. August Pí i Sunyer Research Institute (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain 5. Glaucoma Unit, Institut Clínic d’Oftalmologia, Hospital Clínic, 08036 Barcelona, Spain 6. Glaucoma Unit, Hospital Sagrat Cor. Barcelona, 08029 Barcelona, Spain
Abstract
Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta-blockers (BB) and prostaglandin analogues (PGA). Prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single-nucleotide polymorphisms were genotyped by real-time PCR assays: prostaglandin-F2α receptor (rs3766355, rs3753380); cytochrome-P450 2D6 (rs16947, rs769258); and beta-2-adrenergic receptor (rs1042714). Other studied variables were mean deviation (MD) of visual field, previous ocular interventions, medical treatment, baseline (bIOP), and treated intraocular pressure (tIOP). From a total of 139 eyes, 71 (51.1%) were left eyes. The main diagnosis was primary open angle glaucoma (66.2%). A total of 57 (41%) eyes were under three or more medications (PGA + BB + other) and, additionally, 57 eyes (41%) had had some kind of glaucoma surgery. The mean bIOP and tIOP were 26.55 ± 8.19 and 21.01 ± 5.54 mmHg, respectively. Significant differences in tIOP were found between heterozygous (HT) (21.07 ± 0.607 mmHg) and homozygous (HM) (20.98 ± 0.639 mmHg) rs3766355 with respect to wildtype individuals (16 ± 1.08 mmHg) (p = 0.031). The MD values presented significant differences between wildtype rs3766355 (−2 ± 2.2 dB), HT (−3.87 ± 4 dB), and HM carriers (−9.37 ± 9.51 dB) (p = 0.009). Significant differences were also observed between the MD in wildtype rs3753380 (−6.1 ± 8.67 dB), HT (−9.02 ± 8.63 dB), and HM carriers (−9.51 ± 7.44 dB) (p = 0.017). Patients carrying the variant rs3766355 in HM or HT presented clinically-significantly higher tIOP than wildtype patients. Additionally, some differences in MD were found in rs3766355 and rs3753380 carriers, and the more alleles that were affected, the worse the MD value, meaning greater severity of the glaucoma. Poor response to treatment and more visual field damage may be associated with being a carrier of these mutated alleles.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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