Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome
Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome
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DOI：
10.1016/j.ophtha.2021.11.001
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发表时间：
2022-03-18
期刊：
影响因子：
13.7
通讯作者：
Aung, Tin
中科院分区：
文献类型：
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作者：
Bell, Katharina;Ozaki, Mineo;Aung, Tin
目的：最近有报道称，CYP 39 A1基因功能缺陷突变的携带者患剥脱综合征（XFS）的风险增加2倍。本研究的目的是评估携带CYP 39 A1 G204 E突变的XFS患者与不携带任何CYP 39 A1突变的XFS患者相比的失明风险和相关临床表型。设计：回顾性病例研究。从日本XFS患者中随机选择35例携带CYP 39 A1 G204 E突变的XFS患者和150例不携带任何CYP 39 A1突变的XFS患者，方法：使用α水平< 0.05的双侧Fisher精确检验来估计所有分类测量的计算的优势比（OR）的显著性。使用线性混合效应模型进行受试者组之间的比较，其中组作为随机效应，并考虑受试者内眼睛之间可能的依赖性。主要结果测量：主要分析比较了失明的发生率（定义为视敏度[VA] < 0.05小数），剥脱性青光眼（XFG）的患病率，青光眼手术史，并对CYP 39 A1基因G204 E携带者与非携带者的视野（VF）、平均偏差（MD）、眼内压（IOP）、垂直杯盘比（CDR）等青光眼严重程度指标进行比较。携带CYP 39 A1 G204 E变异的XFS患者失明的总体风险显著较高（10/35 [28.6%]）与无任何CYP 39 A1突变的XFS患者相比（8/150 [5.4%];比值比[OR]，7.1; 95%置信区间[CI]，2.7-20.2]; P < 0.001）。与对照组（41/150 [27.3%]; OR，5.1; 95%CI，2.4-11.4]; P < 0.0001）相比，具有CYP 39 A1 G204 E突变的XFS患者（23/35 [65.7%]）中至少1只眼存在XFG证据的比例更高。CYP 39 A1 G204 E变异携带者的10 P峰值、垂直CDR和VF MD均显著增高（P < 0.001）。此外，CYP 39 A1 G204 E突变患者（18/35 [51.4%]）与无任何CYP 39 A1突变的患者相比，需要更多的激光或青光眼手术干预（32/150 [21.3%]，P < 0.001）。携带CYP 39 A1 G204 E突变的XFS患者失明风险显著增加，XFG发生率较高，与无任何CYP 39 A1突变的XFS患者相比，青光眼更严重。(C)2021年美国眼科学会
Purpose: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation.Design: Retrospective case study.Participants: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort.Methods: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account.Main Outcome Measures: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation.Results: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak 10P, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001).Conclusions: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation. (C) 2021 by the American Academy of Ophthalmology