CYP3A4 Poor and Intermediate Metabolizers Have a Higher Rate of Steroid-Induced Intraocular Pressure Response.

IF 2 4区 医学 Q2 OPHTHALMOLOGY
Journal of Glaucoma Pub Date : 2025-02-01 Epub Date: 2024-08-13 DOI:10.1097/IJG.0000000000002482
Jessica A Wright, Sarah C Xu, Mitchell H Wong, Razan M El Melik, David Hodge, Arthur J Sit
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引用次数: 0

Abstract

Purpose: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroids, and the rate of steroid-induced intraocular pressure (IOP) response.

Materials and methods: Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race, and sex. All subjects had at least 3 eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspects were excluded.

Results: Of the 10,073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mm Hg or more, significantly higher compared with 23% (5/22) of matched controls ( P =0.031). Although more poor/intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups was similar (5.0±2.5 mm Hg in CYP3A4 poor/intermediate metabolizers compared with 4.1±2.1 mm Hg in controls, P =0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P =1.0).

Conclusion: Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation.

"CYP3A4贫代谢者和中间代谢者的类固醇诱发眼压反应率更高"。
目的:评估编码外源性类固醇代谢酶的基因 CYP3A4 表型与类固醇诱导的眼压(IOP)反应率之间的关系:使用 PGRN-Seq 测定法完成了 10073 例患者 CYP3A4 的淋巴细胞 DNA 测序。确定了具有 CYP3A4 中间代谢者或较慢表型的受试者,并与年龄、种族和性别匹配的对照组进行了比较。所有受试者至少接受过三次眼科检查,其中至少一次是在眼部以外的身体任何部位使用局部/全身/局部类固醇时接受的检查。已患青光眼或疑似青光眼的患者被排除在外:在 10073 名患者中,有 63 名患者具有 CYP3A4 贫代谢或中间代谢表型。在这 63 名患者中,22 人有使用类固醇的记录。59%(13/22)的 CYP3A4 差/中间代谢者患者的类固醇诱导眼压反应为 3 mmHg 或更高,明显高于 23%(5/22)的匹配对照组(P=0.031)。虽然更多的类固醇低/中代谢者有类固醇反应,但两组类固醇反应者的平均眼压升高幅度相似(CYP3A4 低/中代谢者为 5.0 ± 2.5 mmHg,对照组为 4.1 ± 2.1 mmHg,P=0.327)。两组患者的青光眼家族史相似(7/22 对 8/22,P=1.0):结论:CYP3A4表型降低可能有助于识别类固醇诱发眼压升高风险较高的患者:这项回顾性研究对CYP3A4基因测序的患者进行了检查,CYP3A4是一种编码外源性类固醇代谢酶的基因。与正常代谢者相比,CYP3A4 贫代谢者或中间代谢者的类固醇引起的眼压反应率更高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Glaucoma
Journal of Glaucoma 医学-眼科学
CiteScore
4.20
自引率
10.00%
发文量
330
审稿时长
4-8 weeks
期刊介绍: The Journal of Glaucoma is a peer reviewed journal addressing the spectrum of issues affecting definition, diagnosis, and management of glaucoma and providing a forum for lively and stimulating discussion of clinical, scientific, and socioeconomic factors affecting care of glaucoma patients.
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