Philipp Hendrix1, Paul M Foreman2, Mark R Harrigan2, Winfield S Fisher2, Nilesh A Vyas3, Robert H Lipsky4, Minkuan Lin5, Beverly C Walters6, R Shane Tubbs7, Mohammadali M Shoja8, Jean-Francois Pittet9, Mali Mathru9, Christoph J Griessenauer10. 1. Department of Neurosurgery, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg/Saar, Germany. Electronic address: hendrix.philipp@gmail.com. 2. Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA. 3. Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA. 4. Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA. 5. Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA. 6. Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA. 7. Seattle Science Foundation, Seattle, Washington, USA. 8. Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 9. Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 10. Department of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Department of Neurosurgery, Geisinger Health System, Danville, Pennsylvania, USA.
Abstract
BACKGROUND: Genetic variations of the serine proteinase inhibitor family E member 1 (SERPINE1) gene, which encodes plasminogen activator inhibitor 1, correlate with serum levels of its product and are associated with thrombophilia and coronary atherosclerosis. Various SERPINE1 ;gene polymorphisms have been identified. However, only the functional 5G/4G polymorphism has been assessed in the context of aneurysmal subarachnoid hemorrhage (aSAH). We assessed associations of 6 SERPINE1 polymorphisms with the clinical sequelae of aSAH. METHODS: From 2012 to 2015, patients with aSAH were prospectively enrolled into the CARAS (Cerebral Aneurysm Renin Angiotensin System) study at 2 major academic institutions. Blood samples were used to evaluate 6 common SERPINE1 single nucleotide polymorphisms via 5' exonuclease (Taqman) genotyping assays. RESULTS: There was an association of the AA genotype of rs2227631 with the 4G/4G genotype and of the GG genotype of rs7242 with the AA genotype of rs2227684. In multivariable analysis, patients with the AA genotype of rs2227631 and 4G/4G genotype had an increased risk for developing delayed cerebral ischemia. Patients with the GG genotype of rs7242 and AA genotype of rs2227684 had a decreased risk for a poor functional outcome. CONCLUSIONS: SERPINE1 gene polymorphisms were associated with delayed cerebral ischemia and functional outcome after aSAH. These associations may arise from alterations of plasminogen activator inhibitor 1 levels.
BACKGROUND: Genetic variations of the serine proteinase inhibitor family E member 1 (SERPINE1) gene, which encodes plasminogen activator inhibitor 1, correlate with serum levels of its product and are associated with thrombophilia and coronary atherosclerosis. Various SERPINE1 ;gene polymorphisms have been identified. However, only the functional 5G/4G polymorphism has been assessed in the context of aneurysmal subarachnoid hemorrhage (aSAH). We assessed associations of 6 SERPINE1 polymorphisms with the clinical sequelae of aSAH. METHODS: From 2012 to 2015, patients with aSAH were prospectively enrolled into the CARAS (Cerebral Aneurysm Renin Angiotensin System) study at 2 major academic institutions. Blood samples were used to evaluate 6 common SERPINE1 single nucleotide polymorphisms via 5' exonuclease (Taqman) genotyping assays. RESULTS: There was an association of the AA genotype of rs2227631 with the 4G/4G genotype and of the GG genotype of rs7242 with the AA genotype of rs2227684. In multivariable analysis, patients with the AA genotype of rs2227631 and 4G/4G genotype had an increased risk for developing delayed cerebral ischemia. Patients with the GG genotype of rs7242 and AA genotype of rs2227684 had a decreased risk for a poor functional outcome. CONCLUSIONS:SERPINE1 gene polymorphisms were associated with delayed cerebral ischemia and functional outcome after aSAH. These associations may arise from alterations of plasminogen activator inhibitor 1 levels.
Authors: Julian V Clarke; Julia M Suggs; Deepti Diwan; Jin V Lee; Kim Lipsey; Ananth K Vellimana; Gregory J Zipfel Journal: J Cereb Blood Flow Metab Date: 2020-04-28 Impact factor: 6.200
Authors: Mingkuan Lin; Christoph J Griessenauer; Robert M Starke; R Shane Tubbs; Mohammadali M Shoja; Paul M Foreman; Nilesh A Vyas; Beverly C Walters; Mark R Harrigan; Philipp Hendrix; Winfield S Fisher; Jean-Francois Pittet; Mali Mathru; Robert H Lipsky Journal: Mol Genet Genomic Med Date: 2019-07-03 Impact factor: 2.183
Authors: Devin W McBride; Spiros L Blackburn; Kumar T Peeyush; Kanako Matsumura; John H Zhang Journal: Front Neurol Date: 2017-10-23 Impact factor: 4.003