Glaucoma Unit, Instituto Oftalmologico Integral, C/María Auxiliadora 25, 08017 Barcelona, Spain.
Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Service, Biomedical Diagnostic Center, Hospital Clinic Barcelona, University of Barcelona, 08007 Barcelona, Spain.
Int J Mol Sci. 2023 Jan 20;24(3):2093. doi: 10.3390/ijms24032093.
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) ( = 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) ( = 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) ( = 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.
对一组青光眼和高眼压患者的表型特征进行预测的基因型分析，以及与他们对β受体阻滞剂（BB）和前列腺素类似物（PGA）的个体药物反应的相关性。这是一项前瞻性研究，包括 72 名接受 BB 和/或 PGA 治疗的患者的 139 只眼睛，在某些情况下还接受了其他类型的眼压低治疗。通过实时 PCR 检测对 5 个单核苷酸多态性进行了基因分型：前列腺素 F2α受体（rs3766355、rs3753380）；细胞色素 P450 2D6（rs16947、rs769258）；β-2-肾上腺素能受体（rs1042714）。其他研究的变量包括视野平均偏差（MD）、以前的眼部干预、药物治疗、基线眼压（bIOP）和治疗眼压（tIOP）。在总共 139 只眼中，71 只（51.1%）为左眼。主要诊断为原发性开角型青光眼（66.2%）。共有 57 只（41%）眼睛接受了三种或三种以上药物治疗（PGA+BB+其他），此外，57 只眼睛（41%）进行了某种青光眼手术。平均 bIOP 和 tIOP 分别为 26.55±8.19mmHg 和 21.01±5.54mmHg。rs3766355 的杂合子（HT）（21.07±0.607mmHg）和纯合子（HM）（20.98±0.639mmHg）与野生型个体（16±1.08mmHg）相比，tIOP 存在显著差异（ = 0.031）。野生型 rs3766355（-2±2.2dB）、HT（-3.87±4dB）和 HM 携带者（-9.37±9.51dB）的 MD 值存在显著差异（ = 0.009）。野生型 rs3753380（-6.1±8.67dB）、HT（-9.02±8.63dB）和 HM 携带者（-9.51±7.44dB）之间也观察到 MD 存在显著差异（ = 0.017）。携带 rs3766355 HM 或 HT 变异的患者的 tIOP 明显高于野生型患者。此外，rs3766355 和 rs3753380 携带者的 MD 也存在差异，受影响的等位基因越多，MD 值越差，青光眼的严重程度越高。治疗反应差和视野损伤可能与携带这些突变等位基因有关。
