Cerebral edema constitutes an important contributor to secondary injury in acute brain injury. The quantification of cerebral edema in neuroimaging, a well-established biomarker of secondary brain injury, represents a useful intermediate phenotype to study edema formation. Population genetics provides powerful tools to identify novel susceptibility genes, biological pathways and therapeutic targets related to brain edema formation. Here, we provide an overview of the pathogenesis of cerebral edema, introduce relevant genetic methods to study this process, and discuss the ongoing research on the genetic underpinnings of edema formation in acute brain injury. The epsilon 2 and 4 variants within the Apolipoprotein E (APOE) gene are associated with worse outcome after traumatic brain injury and intracerebral hemorrhage, and recent studies link these polymorphisms to inflammatory processes that lead to blood-brain barrier disruption and vasogenic edema. For the Haptoglobin gene (HP), the Hp 2−2 genotype associates with worse outcome after acute brain injury, whereas the haptoglobin Hp 1−1 genotype correlates with increased edema in the early phases of intracerebral hemorrhage. Another important protein in cerebral edema is aquaporin 4, coded by the AQP4 gene. AQP4 mutations contribute to the formation of cytotoxic edema, and further genetic research is necessary to help elucidate the mediating mechanism. Findings supporting the target genes outlined above require replication in larger samples and evaluation in non-white populations. These next steps will be significantly facilitated by the rapid changes observed in the field of population genetics, including large international collaborations, open access to genetic data, and significant reductions in the cost of genotyping technologies.

脑水肿是急性脑损伤继发性损伤的重要原因。神经影像学中脑水肿的量化是继发性脑损伤的公认生物标志物，代表了研究水肿形成的有用中间表型。群体遗传学提供了强大的工具来识别与脑水肿形成相关的新的易感基因、生物途径和治疗靶点。在此，我们对脑水肿的发病机制进行概述，介绍相关的遗传学方法来研究这一过程，并讨论正在进行的关于急性脑损伤水肿形成的遗传基础的研究。载脂蛋白 E (APOE) 基因内的 epsilon 2 和 4 变异与创伤性脑损伤和脑出血后的较差预后相关，最近的研究将这些多态性与导致血脑屏障破坏和血管源性水肿的炎症过程联系起来。对于触珠蛋白基因 ( HP )，Hp 2−2 基因型与急性脑损伤后较差的预后相关，而触珠蛋白 Hp 1−1 基因型与脑出血早期水肿增加相关。脑水肿中另一个重要的蛋白质是水通道蛋白4，由AQP4基因编码。AQP4突变导致细胞毒性水肿的形成，需要进一步的基因研究来帮助阐明其介导机制。支持上述目标基因的发现需要在更大的样本中复制并在非白人群体中进行评估。群体遗传学领域观察到的快速变化将极大促进接下来的步骤，包括大型国际合作、遗传数据的开放获取以及基因分型技术成本的大幅降低。