Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and 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

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)672-677
Number of pages6
JournalWorld Neurosurgery
Volume105
DOIs
StatePublished - Sep 1 2017
Externally publishedYes

Fingerprint

Serine Proteinase Inhibitors
Plasminogen Activator Inhibitor 1
Subarachnoid Hemorrhage
Genotype
Brain Ischemia
Phosphodiesterase I
Genes
Thrombophilia
Intracranial Aneurysm
Renin-Angiotensin System
Single Nucleotide Polymorphism
Coronary Artery Disease
Serum

Keywords

  • Aneurysm
  • Delayed cerebral ischemia
  • Outcome
  • Plasminogen activator inhibitor 1
  • Polymorphism
  • SERPINE1
  • Subarachnoid hemorrhage
  • Vasospasm

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). Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage. World Neurosurgery, 105, 672-677. https://doi.org/10.1016/j.wneu.2017.05.175

Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and 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. 105, 01.09.2017, p. 672-677.

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, 'Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage', World Neurosurgery, vol. 105, pp. 672-677. https://doi.org/10.1016/j.wneu.2017.05.175
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. / Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage. In: World Neurosurgery. 2017 ; Vol. 105. pp. 672-677.
@article{59bdde6b8e654550bc5460c2ab973737,
title = "Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage",
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.",
keywords = "Aneurysm, Delayed cerebral ischemia, Outcome, Plasminogen activator inhibitor 1, Polymorphism, SERPINE1, Subarachnoid hemorrhage, Vasospasm",
author = "Philipp Hendrix and Foreman, {Paul M.} and Harrigan, {Mark R.} and Fisher, {Winfield S.} and Vyas, {Nilesh A.} and Lipsky, {Robert H.} and Minkuan Lin and Walters, {Beverly C.} and Tubbs, {R. Shane} and {Mohajel Shoja}, Mohammadali and Pittet, {Jean Francois} and Mali Mathru and Griessenauer, {Christoph J.}",
year = "2017",
month = "9",
day = "1",
doi = "10.1016/j.wneu.2017.05.175",
language = "English (US)",
volume = "105",
pages = "672--677",
journal = "World Neurosurgery",
issn = "1878-8750",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage

AU - Hendrix, Philipp

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.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - Aneurysm

KW - Delayed cerebral ischemia

KW - Outcome

KW - Plasminogen activator inhibitor 1

KW - Polymorphism

KW - SERPINE1

KW - Subarachnoid hemorrhage

KW - Vasospasm

UR - http://www.scopus.com/inward/record.url?scp=85021699710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021699710&partnerID=8YFLogxK

U2 - 10.1016/j.wneu.2017.05.175

DO - 10.1016/j.wneu.2017.05.175

M3 - Article

C2 - 28599907

AN - SCOPUS:85021699710

VL - 105

SP - 672

EP - 677

JO - World Neurosurgery

JF - World Neurosurgery

SN - 1878-8750

ER -