Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage

Christoph J. Griessenauer, R. Shane Tubbs, Paul M. Foreman, Michelle H. Chua, Nilesh A. Vyas, Robert H. Lipsky, Mingkuan Lin, Ramaswamy Iyer, Rishikesh Haridas, Beverly C. Walters, Salman Chaudry, Aisana Malieva, Samantha Wilkins, Mark R. Harrigan, Winfeld S. Fisher, Mohammadali Mohajel Shoja

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients and controls at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensinconverting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5' exonuclease (TaqMan) genotyping assays and restriction fragment length polymorphism analysis. RESULTS Two hundred forty-eight patients were screened, and 149 aSAH patients and 50 controls were available for analysis. There was a recessive effect of the C allele of the angiotensinogen (AGT) C/T single-nucleotide polymorphism (SNP) (OR 1.94, 95% CI 0.912-4.12, p = 0.0853) and a dominant effect of the G allele of the angiotensin II receptor Type 2 (AT2) G/A SNP (OR 2.11, 95% CI 0.972-4.57, p = 0.0590) on aSAH that did not reach statistical signifcance after adjustment for potential confounders. The ACE level was signifcantly lower in aSAH patients with the II genotype (17.6 ± 8.0 U/L) as compared with the ID (22.5 ± 12.1 U/L) and DD genotypes (26.6 ± 14.2 U/L) (p = 0.0195). CONCLUSIONS The AGT C/T and AT2 G/A polymorphisms were not signifcantly associated with aSAH after controlling for potential confounders. However, a strong trend was identifed for a dominant effect of the G allele of the AT2 G/A SNP. Downregulation of the local RAS may contribute to the formation of cerebral aneurysms and subsequent presentation with aSAH. Further studies are required to elucidate the relevant pathophysiology and its potential implication in treatment of patients with aSAH.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalJournal of Neurosurgery
Volume128
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Genetic Polymorphisms
Subarachnoid Hemorrhage
Renin-Angiotensin System
Intracranial Aneurysm
Single Nucleotide Polymorphism
Angiotensinogen
Alleles
Genotype
Phosphodiesterase I
Angiotensin Type 2 Receptor
Enzymes
Restriction Fragment Length Polymorphisms
Rupture
Down-Regulation

Keywords

  • Angiotensin
  • Cerebral aneurysm
  • Renin
  • Rupture
  • Subarachnoid hemorrhage
  • Vascular disorders

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Griessenauer, C. J., Shane Tubbs, R., Foreman, P. M., Chua, M. H., Vyas, N. A., Lipsky, R. H., ... Mohajel Shoja, M. (2018). Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage. Journal of Neurosurgery, 128(1), 86-93. https://doi.org/10.3171/2016.9.JNS161593

Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage. / Griessenauer, Christoph J.; Shane Tubbs, R.; Foreman, Paul M.; Chua, Michelle H.; Vyas, Nilesh A.; Lipsky, Robert H.; Lin, Mingkuan; Iyer, Ramaswamy; Haridas, Rishikesh; Walters, Beverly C.; Chaudry, Salman; Malieva, Aisana; Wilkins, Samantha; Harrigan, Mark R.; Fisher, Winfeld S.; Mohajel Shoja, Mohammadali.

In: Journal of Neurosurgery, Vol. 128, No. 1, 01.01.2018, p. 86-93.

Research output: Contribution to journalArticle

Griessenauer, CJ, Shane Tubbs, R, Foreman, PM, Chua, MH, Vyas, NA, Lipsky, RH, Lin, M, Iyer, R, Haridas, R, Walters, BC, Chaudry, S, Malieva, A, Wilkins, S, Harrigan, MR, Fisher, WS & Mohajel Shoja, M 2018, 'Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage', Journal of Neurosurgery, vol. 128, no. 1, pp. 86-93. https://doi.org/10.3171/2016.9.JNS161593
Griessenauer, Christoph J. ; Shane Tubbs, R. ; Foreman, Paul M. ; Chua, Michelle H. ; Vyas, Nilesh A. ; Lipsky, Robert H. ; Lin, Mingkuan ; Iyer, Ramaswamy ; Haridas, Rishikesh ; Walters, Beverly C. ; Chaudry, Salman ; Malieva, Aisana ; Wilkins, Samantha ; Harrigan, Mark R. ; Fisher, Winfeld S. ; Mohajel Shoja, Mohammadali. / Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage. In: Journal of Neurosurgery. 2018 ; Vol. 128, No. 1. pp. 86-93.
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abstract = "OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients and controls at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensinconverting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5' exonuclease (TaqMan) genotyping assays and restriction fragment length polymorphism analysis. RESULTS Two hundred forty-eight patients were screened, and 149 aSAH patients and 50 controls were available for analysis. There was a recessive effect of the C allele of the angiotensinogen (AGT) C/T single-nucleotide polymorphism (SNP) (OR 1.94, 95{\%} CI 0.912-4.12, p = 0.0853) and a dominant effect of the G allele of the angiotensin II receptor Type 2 (AT2) G/A SNP (OR 2.11, 95{\%} CI 0.972-4.57, p = 0.0590) on aSAH that did not reach statistical signifcance after adjustment for potential confounders. The ACE level was signifcantly lower in aSAH patients with the II genotype (17.6 ± 8.0 U/L) as compared with the ID (22.5 ± 12.1 U/L) and DD genotypes (26.6 ± 14.2 U/L) (p = 0.0195). CONCLUSIONS The AGT C/T and AT2 G/A polymorphisms were not signifcantly associated with aSAH after controlling for potential confounders. However, a strong trend was identifed for a dominant effect of the G allele of the AT2 G/A SNP. Downregulation of the local RAS may contribute to the formation of cerebral aneurysms and subsequent presentation with aSAH. Further studies are required to elucidate the relevant pathophysiology and its potential implication in treatment of patients with aSAH.",
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author = "Griessenauer, {Christoph J.} and {Shane Tubbs}, R. and Foreman, {Paul M.} and Chua, {Michelle H.} and Vyas, {Nilesh A.} and Lipsky, {Robert H.} and Mingkuan Lin and Ramaswamy Iyer and Rishikesh Haridas and Walters, {Beverly C.} and Salman Chaudry and Aisana Malieva and Samantha Wilkins and Harrigan, {Mark R.} and Fisher, {Winfeld S.} and {Mohajel Shoja}, Mohammadali",
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T1 - Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage

AU - Griessenauer, Christoph J.

AU - Shane Tubbs, R.

AU - Foreman, Paul M.

AU - Chua, Michelle H.

AU - Vyas, Nilesh A.

AU - Lipsky, Robert H.

AU - Lin, Mingkuan

AU - Iyer, Ramaswamy

AU - Haridas, Rishikesh

AU - Walters, Beverly C.

AU - Chaudry, Salman

AU - Malieva, Aisana

AU - Wilkins, Samantha

AU - Harrigan, Mark R.

AU - Fisher, Winfeld S.

AU - Mohajel Shoja, Mohammadali

PY - 2018/1/1

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N2 - OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients and controls at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensinconverting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5' exonuclease (TaqMan) genotyping assays and restriction fragment length polymorphism analysis. RESULTS Two hundred forty-eight patients were screened, and 149 aSAH patients and 50 controls were available for analysis. There was a recessive effect of the C allele of the angiotensinogen (AGT) C/T single-nucleotide polymorphism (SNP) (OR 1.94, 95% CI 0.912-4.12, p = 0.0853) and a dominant effect of the G allele of the angiotensin II receptor Type 2 (AT2) G/A SNP (OR 2.11, 95% CI 0.972-4.57, p = 0.0590) on aSAH that did not reach statistical signifcance after adjustment for potential confounders. The ACE level was signifcantly lower in aSAH patients with the II genotype (17.6 ± 8.0 U/L) as compared with the ID (22.5 ± 12.1 U/L) and DD genotypes (26.6 ± 14.2 U/L) (p = 0.0195). CONCLUSIONS The AGT C/T and AT2 G/A polymorphisms were not signifcantly associated with aSAH after controlling for potential confounders. However, a strong trend was identifed for a dominant effect of the G allele of the AT2 G/A SNP. Downregulation of the local RAS may contribute to the formation of cerebral aneurysms and subsequent presentation with aSAH. Further studies are required to elucidate the relevant pathophysiology and its potential implication in treatment of patients with aSAH.

AB - OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients and controls at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensinconverting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5' exonuclease (TaqMan) genotyping assays and restriction fragment length polymorphism analysis. RESULTS Two hundred forty-eight patients were screened, and 149 aSAH patients and 50 controls were available for analysis. There was a recessive effect of the C allele of the angiotensinogen (AGT) C/T single-nucleotide polymorphism (SNP) (OR 1.94, 95% CI 0.912-4.12, p = 0.0853) and a dominant effect of the G allele of the angiotensin II receptor Type 2 (AT2) G/A SNP (OR 2.11, 95% CI 0.972-4.57, p = 0.0590) on aSAH that did not reach statistical signifcance after adjustment for potential confounders. The ACE level was signifcantly lower in aSAH patients with the II genotype (17.6 ± 8.0 U/L) as compared with the ID (22.5 ± 12.1 U/L) and DD genotypes (26.6 ± 14.2 U/L) (p = 0.0195). CONCLUSIONS The AGT C/T and AT2 G/A polymorphisms were not signifcantly associated with aSAH after controlling for potential confounders. However, a strong trend was identifed for a dominant effect of the G allele of the AT2 G/A SNP. Downregulation of the local RAS may contribute to the formation of cerebral aneurysms and subsequent presentation with aSAH. Further studies are required to elucidate the relevant pathophysiology and its potential implication in treatment of patients with aSAH.

KW - Angiotensin

KW - Cerebral aneurysm

KW - Renin

KW - Rupture

KW - Subarachnoid hemorrhage

KW - Vascular disorders

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