medRxiv : the preprint server for health sciences · 2025
Pharmacogenomics of steroid-induced ocular hypertension: relationship to high-tension glaucomas and new pathophysiologic insight.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Song Zeyuan, Pany Satyabrata, Guo Shengru, Mazumder Arpan G, Itakura Tatsuo, Huang Jonathan, Magarychoff Evan, Gurinovich Anastasia, Benchek Penelope H, Stamer W Daniel, Price Francis W, Willoughby Colin E, Senthilkumari Srinivasan, George Ronnie J, Chitipothu Srujana, Lass Jonathan H, Iyengar Sudha K, Schwartz Stephen G, Griswold Anthony J, Sebastiani Paola, Price Marianne O, Fini M Elizabeth
Аннотация
Adverse drug reactions are a frequent cause of worldwide morbidity and mortality. Glucocorticoids (GCs), commonly used to treat inflammatory diseases, alter gene expression with both beneficial and adverse consequences. When used in the eye, GCs cause steroid-induced ocular hypertension (SIOH) in 30-50% of patients, leading to steroid-induced glaucoma. Evidence suggests that predisposition to SIOH is genetically determined. Here we took a pharmacogenomic approach to discover DNA variants associated with SIOH. We identified 44 SNPs of genome-wide significance (p<5E-08) located at 26 risk loci out of a total of 531 SNPs of suggestive significance (p<5E-06) at 262 risk loci. Unlike SNPs identified in complex disease which are overwhelmingly common in frequency, most SNPs found here were rare or of low frequency, likely discoverable because of their large effect sizes. Follow-up analyses provide insight into the pathogenetic relationship of SIOH to high-tension glaucomas and suggest a new mechanistic paradigm for SIOH pathophysiology.