Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Philipp Hendrix, Paul M. Foreman, Mark R. Harrigan, Winfield S. Fisher, Nilesh A. Vyas, Robert H. Lipsky, Minkuan Lin, Beverly C. Walters, R. Shane Tubbs, Mohammadali Mohajel Shoja, Jean Francois Pittet, Mali Mathru, Christoph J. Griessenauer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and Objective The high-mobility group box 1 (HMGB1) protein is a 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), increased 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 Patients with aSAH and controls enrolled in the prospective, 2-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 patients with aSAH and controls. Associations between aSAH and its clinical sequelae with the HMGB1 SNP were assessed. Results Samples from 149 patients with aSAH and 50 controls were available for analysis. No increased risk for aSAH associated with the SNP was found compared with the control group. Delayed cerebral ischemia (DCI) was defined as a cerebral infarction at the time of discharge from the intensive care unit and identified in 21.2% of patients with aSAH. In multivariable logistic regression analysis, the G allele of rs2249825 was independently associated with DCI (odds ratio, 5.695; 95% confidence interval, 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, after aSAH. This finding may be attributable to an increased HMGB1 protein expression in these patients.

Original languageEnglish (US)
Pages (from-to)325-330
Number of pages6
JournalWorld Neurosurgery
Volume101
DOIs
StatePublished - May 1 2017
Externally publishedYes

Fingerprint

Subarachnoid Hemorrhage
Brain Ischemia
HMGB1 Protein
Single Nucleotide Polymorphism
Cerebral Infarction
Alleles
Intracranial Vasospasm
Intracranial Aneurysm
Renin-Angiotensin System
Intensive Care Units
Biomarkers
Logistic Models
Odds Ratio
Regression Analysis
Confidence Intervals
Control Groups
Wounds and Injuries

Keywords

  • Aneurysm
  • Delayed cerebral ischemia
  • High-mobility group box 1
  • Outcome
  • Polymorphism
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Hendrix, P., Foreman, P. M., Harrigan, M. R., Fisher, W. S., Vyas, N. A., Lipsky, R. H., ... Griessenauer, C. J. (2017). Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. World Neurosurgery, 101, 325-330. https://doi.org/10.1016/j.wneu.2017.01.121

Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. / Hendrix, Philipp; Foreman, Paul M.; Harrigan, Mark R.; Fisher, Winfield S.; Vyas, Nilesh A.; Lipsky, Robert H.; Lin, Minkuan; Walters, Beverly C.; Tubbs, R. Shane; Mohajel Shoja, Mohammadali; Pittet, Jean Francois; Mathru, Mali; Griessenauer, Christoph J.

In: World Neurosurgery, Vol. 101, 01.05.2017, p. 325-330.

Research output: Contribution to journalArticle

Hendrix, P, Foreman, PM, Harrigan, MR, Fisher, WS, Vyas, NA, Lipsky, RH, Lin, M, Walters, BC, Tubbs, RS, Mohajel Shoja, M, Pittet, JF, Mathru, M & Griessenauer, CJ 2017, 'Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage', World Neurosurgery, vol. 101, pp. 325-330. https://doi.org/10.1016/j.wneu.2017.01.121
Hendrix, Philipp ; Foreman, Paul M. ; Harrigan, Mark R. ; Fisher, Winfield S. ; Vyas, Nilesh A. ; Lipsky, Robert H. ; Lin, Minkuan ; Walters, Beverly C. ; Tubbs, R. Shane ; Mohajel Shoja, Mohammadali ; Pittet, Jean Francois ; Mathru, Mali ; Griessenauer, Christoph J. / Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. In: World Neurosurgery. 2017 ; Vol. 101. pp. 325-330.
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abstract = "Background and Objective The high-mobility group box 1 (HMGB1) protein is a 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), increased 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 Patients with aSAH and controls enrolled in the prospective, 2-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 patients with aSAH and controls. Associations between aSAH and its clinical sequelae with the HMGB1 SNP were assessed. Results Samples from 149 patients with aSAH and 50 controls were available for analysis. No increased risk for aSAH associated with the SNP was found compared with the control group. Delayed cerebral ischemia (DCI) was defined as a cerebral infarction at the time of discharge from the intensive care unit and identified in 21.2{\%} of patients with aSAH. In multivariable logistic regression analysis, the G allele of rs2249825 was independently associated with DCI (odds ratio, 5.695; 95{\%} confidence interval, 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, after aSAH. This finding may be attributable to an increased HMGB1 protein expression in these patients.",
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AU - Foreman, Paul M.

AU - Harrigan, Mark R.

AU - Fisher, Winfield S.

AU - Vyas, Nilesh A.

AU - Lipsky, Robert H.

AU - Lin, Minkuan

AU - Walters, Beverly C.

AU - Tubbs, R. Shane

AU - Mohajel Shoja, Mohammadali

AU - Pittet, Jean Francois

AU - Mathru, Mali

AU - Griessenauer, Christoph J.

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AB - Background and Objective The high-mobility group box 1 (HMGB1) protein is a 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), increased 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 Patients with aSAH and controls enrolled in the prospective, 2-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 patients with aSAH and controls. Associations between aSAH and its clinical sequelae with the HMGB1 SNP were assessed. Results Samples from 149 patients with aSAH and 50 controls were available for analysis. No increased risk for aSAH associated with the SNP was found compared with the control group. Delayed cerebral ischemia (DCI) was defined as a cerebral infarction at the time of discharge from the intensive care unit and identified in 21.2% of patients with aSAH. In multivariable logistic regression analysis, the G allele of rs2249825 was independently associated with DCI (odds ratio, 5.695; 95% confidence interval, 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, after aSAH. This finding may be attributable to an increased HMGB1 protein expression in these patients.

KW - Aneurysm

KW - Delayed cerebral ischemia

KW - High-mobility group box 1

KW - Outcome

KW - Polymorphism

KW - Subarachnoid hemorrhage

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