Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.
Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.
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DOI：
10.1016/j.preteyeres.2016.09.003
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发表时间：
2017-01
影响因子：
17.8
通讯作者：
Stamer WD
中科院分区：
文献类型：
--
作者：
Fini ME;Schwartz SG;Gao X;Jeong S;Patel N;Itakura T;Price MO;Price FW Jr;Varma R;Stamer WD
由于糖皮质激素的治疗性使用引起的眼内压（IOP）升高称为类固醇诱导的高眼压（SIOH）;这可能导致类固醇诱导的青光眼（SIG）。糖皮质激素启动信号级联，最终影响数百个基因的表达;这为高度个性化的药理学反应提供了可能。试图确定遗传风险因素的研究在糖皮质激素使用的早期就进行了，但当时可用的科学工具有限，进展停滞不前。相比之下，在随后的几年里，在定义疾病病理生理学方面取得了重大进展。随着基因组学时代的到来，似乎是时候重新研究遗传学了。药物基因组学是一种无偏见的发现方法，不需要潜在的假设，并提供了一种方法来确定临床上重要的基因和途径，不能被发现任何其他方式。第一个全基因组关联研究的结果，以确定与SIOH相关的多态性，并随访两个新的基因与疾病，GPR 158和HCG 22，在文章的后半部分进行了讨论。然而，决定眼睛对类固醇反应的遗传变异的知识本身也具有作为预测和诊断工具的价值。本文最后讨论了美国总统奥巴马在2015年国情咨文中宣布的精准医学倡议®如何开始触及眼科实践。有人认为，SIOH/SIG可能为精准医学的有效应用提供下一个机会。
Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.