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

IF 2 4区 医学 Q2 OPHTHALMOLOGY
Jessica A Wright, Sarah C Xu, Mitchell H Wong, Razan M El Melik, David Hodge, Arthur J Sit
{"title":"\"CYP3A4 Poor and Intermediate Metabolizers Have a Higher Rate of Steroid-Induced Intraocular Pressure Response\".","authors":"Jessica A Wright, Sarah C Xu, Mitchell H Wong, Razan M El Melik, David Hodge, Arthur J Sit","doi":"10.1097/IJG.0000000000002482","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroid, and the rate of steroid-induced intraocular pressure (IOP) response.</p><p><strong>Materials and methods: </strong>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 three 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 suspect were excluded.</p><p><strong>Results: </strong>Of the 10073 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 mmHg or more, significantly higher compared to 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 were similar (5.0 ± 2.5 mmHg in CYP3A4 poor/intermediate metabolizers compared to 4.1 ± 2.1mmHg in controls, P=0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P=1.0).</p><p><strong>Conclusion: </strong>Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation.</p><p><strong>Prcis: </strong>This retrospective study examined patients with sequenced CYP3A4, a gene encoding an enzyme that metabolizes exogenous steroids. When compared to normal metabolizers, CYP3A4 poor or intermediate metabolizers have a higher steroid-induced IOP response rate.</p>","PeriodicalId":15938,"journal":{"name":"Journal of Glaucoma","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Glaucoma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/IJG.0000000000002482","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroid, 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 three 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 suspect were excluded.

Results: Of the 10073 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 mmHg or more, significantly higher compared to 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 were similar (5.0 ± 2.5 mmHg in CYP3A4 poor/intermediate metabolizers compared to 4.1 ± 2.1mmHg 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.

Prcis: This retrospective study examined patients with sequenced CYP3A4, a gene encoding an enzyme that metabolizes exogenous steroids. When compared to normal metabolizers, CYP3A4 poor or intermediate metabolizers have a higher steroid-induced IOP response rate.

"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。
求助全文
约1分钟内获得全文 求助全文
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信