Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage

Philipp Hendrix, Paul M. Foreman, Mark R. Harrigan, Winfield S. Fisher, Nilesh A. Vyas, Robert H. Lipsky, Mingkuan 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

OBJECTIVE Cystathionine b-synthase (CBS) is involved in homocysteine and hydrogen sulfide (H2S) metabolism. Both products have been implicated in the pathophysiology of cerebrovascular diseases. The impact of CBS polymorphisms on aneurysmal subarachnoid hemorrhage (aSAH) and its clinical sequelae is poorly understood. METHODS Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The CARAS study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012 to 2015. Common CBS polymorphisms were detected using 5'exonuclease genotyping assays. Analysis of associations between CBS polymorphisms and aSAH was performed. RESULTS Samples from 149 aSAH patients and 50 controls were available for analysis. In multivariate logistic regression analysis, the insertion allele of the 844ins68 CBS insertion polymorphism showed a dominant effect on aSAH. The GG genotype of the CBS G/A single nucleotide polymorphism (rs234706) was independently associated with unfavorable functional outcome (modified Rankin Scale Score 3-6) at discharge and last follow-up, but not clinical vasospasm or delayed cerebral ischemia (DCI). CONCLUSIONS The insertion allele of the 844ins68 CBS insertion polymorphism was independently associated with aSAH while the GG genotype of rs234706 was associated with an unfavorable outcome both at discharge and last follow-up. Increased CBS activity may exert its neuroprotective effects through alteration of H2S levels, and independent of clinical vasospasm and DCI.

Original languageEnglish (US)
Pages (from-to)1771-1777
Number of pages7
JournalJournal of neurosurgery
Volume128
Issue number6
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Fingerprint

Cystathionine
Cystathionine beta-Synthase
Subarachnoid Hemorrhage
Intracranial Aneurysm
Renin-Angiotensin System
Brain Ischemia
Alleles
Genotype
Phosphodiesterase I
Cerebrovascular Disorders
Hydrogen Sulfide
Neuroprotective Agents
Homocysteine
Single Nucleotide Polymorphism
Logistic Models
Regression Analysis

Keywords

  • Aneurysm
  • Cystathionine beta-synthase
  • Outcome
  • Polymorphism
  • Subarachnoid hemorrhage
  • Vascular disorders

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. (2018). Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage. Journal of neurosurgery, 128(6), 1771-1777. https://doi.org/10.3171/2017.2.JNS162933

Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage. / Hendrix, Philipp; Foreman, Paul M.; Harrigan, Mark R.; Fisher, Winfield S.; Vyas, Nilesh A.; Lipsky, Robert H.; Lin, Mingkuan; Walters, Beverly C.; Tubbs, R. Shane; Mohajel Shoja, Mohammadali; Pittet, Jean Francois; Mathru, Mali; Griessenauer, Christoph J.

In: Journal of neurosurgery, Vol. 128, No. 6, 01.06.2018, p. 1771-1777.

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 2018, 'Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage', Journal of neurosurgery, vol. 128, no. 6, pp. 1771-1777. https://doi.org/10.3171/2017.2.JNS162933
Hendrix P, Foreman PM, Harrigan MR, Fisher WS, Vyas NA, Lipsky RH et al. Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage. Journal of neurosurgery. 2018 Jun 1;128(6):1771-1777. https://doi.org/10.3171/2017.2.JNS162933
Hendrix, Philipp ; Foreman, Paul M. ; Harrigan, Mark R. ; Fisher, Winfield S. ; Vyas, Nilesh A. ; Lipsky, Robert H. ; Lin, Mingkuan ; Walters, Beverly C. ; Tubbs, R. Shane ; Mohajel Shoja, Mohammadali ; Pittet, Jean Francois ; Mathru, Mali ; Griessenauer, Christoph J. / Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage. In: Journal of neurosurgery. 2018 ; Vol. 128, No. 6. pp. 1771-1777.
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abstract = "OBJECTIVE Cystathionine b-synthase (CBS) is involved in homocysteine and hydrogen sulfide (H2S) metabolism. Both products have been implicated in the pathophysiology of cerebrovascular diseases. The impact of CBS polymorphisms on aneurysmal subarachnoid hemorrhage (aSAH) and its clinical sequelae is poorly understood. METHODS Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The CARAS study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012 to 2015. Common CBS polymorphisms were detected using 5'exonuclease genotyping assays. Analysis of associations between CBS polymorphisms and aSAH was performed. RESULTS Samples from 149 aSAH patients and 50 controls were available for analysis. In multivariate logistic regression analysis, the insertion allele of the 844ins68 CBS insertion polymorphism showed a dominant effect on aSAH. The GG genotype of the CBS G/A single nucleotide polymorphism (rs234706) was independently associated with unfavorable functional outcome (modified Rankin Scale Score 3-6) at discharge and last follow-up, but not clinical vasospasm or delayed cerebral ischemia (DCI). CONCLUSIONS The insertion allele of the 844ins68 CBS insertion polymorphism was independently associated with aSAH while the GG genotype of rs234706 was associated with an unfavorable outcome both at discharge and last follow-up. Increased CBS activity may exert its neuroprotective effects through alteration of H2S levels, and independent of clinical vasospasm and DCI.",
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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, Mingkuan

AU - Walters, Beverly C.

AU - Tubbs, R. Shane

AU - Mohajel Shoja, Mohammadali

AU - Pittet, Jean Francois

AU - Mathru, Mali

AU - Griessenauer, Christoph J.

PY - 2018/6/1

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N2 - OBJECTIVE Cystathionine b-synthase (CBS) is involved in homocysteine and hydrogen sulfide (H2S) metabolism. Both products have been implicated in the pathophysiology of cerebrovascular diseases. The impact of CBS polymorphisms on aneurysmal subarachnoid hemorrhage (aSAH) and its clinical sequelae is poorly understood. METHODS Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The CARAS study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012 to 2015. Common CBS polymorphisms were detected using 5'exonuclease genotyping assays. Analysis of associations between CBS polymorphisms and aSAH was performed. RESULTS Samples from 149 aSAH patients and 50 controls were available for analysis. In multivariate logistic regression analysis, the insertion allele of the 844ins68 CBS insertion polymorphism showed a dominant effect on aSAH. The GG genotype of the CBS G/A single nucleotide polymorphism (rs234706) was independently associated with unfavorable functional outcome (modified Rankin Scale Score 3-6) at discharge and last follow-up, but not clinical vasospasm or delayed cerebral ischemia (DCI). CONCLUSIONS The insertion allele of the 844ins68 CBS insertion polymorphism was independently associated with aSAH while the GG genotype of rs234706 was associated with an unfavorable outcome both at discharge and last follow-up. Increased CBS activity may exert its neuroprotective effects through alteration of H2S levels, and independent of clinical vasospasm and DCI.

AB - OBJECTIVE Cystathionine b-synthase (CBS) is involved in homocysteine and hydrogen sulfide (H2S) metabolism. Both products have been implicated in the pathophysiology of cerebrovascular diseases. The impact of CBS polymorphisms on aneurysmal subarachnoid hemorrhage (aSAH) and its clinical sequelae is poorly understood. METHODS Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The CARAS study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012 to 2015. Common CBS polymorphisms were detected using 5'exonuclease genotyping assays. Analysis of associations between CBS polymorphisms and aSAH was performed. RESULTS Samples from 149 aSAH patients and 50 controls were available for analysis. In multivariate logistic regression analysis, the insertion allele of the 844ins68 CBS insertion polymorphism showed a dominant effect on aSAH. The GG genotype of the CBS G/A single nucleotide polymorphism (rs234706) was independently associated with unfavorable functional outcome (modified Rankin Scale Score 3-6) at discharge and last follow-up, but not clinical vasospasm or delayed cerebral ischemia (DCI). CONCLUSIONS The insertion allele of the 844ins68 CBS insertion polymorphism was independently associated with aSAH while the GG genotype of rs234706 was associated with an unfavorable outcome both at discharge and last follow-up. Increased CBS activity may exert its neuroprotective effects through alteration of H2S levels, and independent of clinical vasospasm and DCI.

KW - Aneurysm

KW - Cystathionine beta-synthase

KW - Outcome

KW - Polymorphism

KW - Subarachnoid hemorrhage

KW - Vascular disorders

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