Genetic Variants Associated With Intraparenchymal Hemorrhage Progression After Traumatic Brain Injury

作者：Ruchira M. Jha, Benjamin E. Zusman, Ava M. Puccio, David O. Okonkwo, Matthew Pease, Shashvat M. Desai, Matthew R. Leach, Yvette P. Conley, Patrick M. Kochanek · 发表于：JAMA Network Open · 年份：2021 · DOI：10.1001/jamanetworkopen.2021.16839 · 被引用次数：22 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Intracerebral and Subarachnoid Hemorrhage Research、S100 Proteins and Annexins

Importance: Intracerebral hemorrhage progression is associated with unfavorable outcome after traumatic brain injury (TBI). No effective treatments are currently available. This secondary injury process reflects an extreme form of vasogenic edema and blood-brain barrier breakdown. The sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) cation channel is a key underlying mechanism. A phase 2 trial of SUR1-TRPM4 inhibition in contusional TBI is ongoing, and a phase 3 trial is being designed. Targeted identification of patients at increased risk for hemorrhage progression may inform prognostication, trial design (including patient selection), and ultimately treatment response. Objective: To determine whether ABCC8 (SUR1) and TRPM4 genetic variability are associated with intraparenchymal hemorrhage (IPH) progression after severe TBI, based on the putative involvement of the SUR1-TRPM4 channel in this pathophysiology. Design, Setting, and Participants: In this genetic association study, DNA was extracted from 416 patients with severe TBI prospectively enrolled from a level I trauma academic medical center from May 9, 2002, to August 8, 2014. Forty ABCC8 and TRPM4 single-nucleotide variants (SNVs) were genotyped (multiplex, unbiased). Data were analyzed from January 7, 2020, to May 3, 2021. Main Outcomes and Measures: Primary analyses addressed IPH progression at 6, 24, and 120 hours in patients without acute craniectomy (n = 321). Multivariable regressio...