Impact of high-mobility group box-1 polymorphism on delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage

Abstract Background and Purpose: The high-mobility group box-1 protein (HMGB1) is an eukaryotic, ubiquitously expressed protein that serves as a biomarker for various diseases and is involved in the promotion of a proinflammatory response to cell injury. In aneurysmal subarachnoid hemorrhage (aSAH), elevated HMGB1 levels have been linked to poor outcome and an increased risk for cerebral vasospasm. The role of HMGB1 polymorphisms in aSAH has not been previously investigated. Methods Aneurysmal subarachnoid hemorrhage patients and controls enrolled in the prospective, two-center CARAS (Cerebral Aneurysm Renin Angiotensin System) study were evaluated. The 3814 C/G HMGB1 single nucleotide polymorphism (SNP) rs2249825 was detected using 5’exonuclease (Taqman) genotyping assays from blood samples from aSAH patients and controls. Associations between aSAH and its clinical sequelae with the HMGB1 SNP were assessed. Results Samples from 149 aSAH patients and 50 controls were available for analysis. No increased risk for aSAH associated with the SNP was found compared to the control group. Delayed cerebral ischemia (DCI) was defined as a cerebral infarction at the time of discharge from the ICU and identified in 21.2% of aSAH patients. In multivariable logistic regression analysis, the G allele of rs2249825 was independently associated with DCI (OR = 5.695, 95% CI 1.804 – 17.975, p = 0.003). Conclusions The minor allele G of rs2249825 was associated with an increased risk for DCI, or cerebral infarction, following aSAH. This may be attributable to an increased HMGB1 protein expression in these patients.