Artikel
Association of cystathionine beta synthase polymorphisms and functional outcome following aneurysmal subarachnoid hemorrhage
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Autoren
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Philipp Hendrix
- Klinik für Neurochirurgie, Universitätsklinik des Saarlandes, Homburg/Saar, Germany, Homburg/Saar, Deutschland
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Paul M. Foreman
- Department of Neurosurgery, University of Alabama at Birmingham, AL, Birmingham, United States
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Mark R. Harrigan
- Department of Neurosurgery, University of Alabama at Birmingham, AL, Birmingham, United States
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Jean-Francois Pittet
- Department of Anesthesiology, University of Alabama at Birmingham, AL, Birmingham, United States
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Mali Mathru
- Department of Anesthesiology, University of Alabama at Birmingham, AL, Birmingham, United States
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Christoph J. Griessenauer
- Department of Neurosurgery, Geisinger Health System, Danville, PA, United States; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, Boston, United States
| Veröffentlicht: | 9. Juni 2017 |
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Gliederung
Text
Objective: Cystathionine β-synthase (CBS) is an enzyme of the transsulfuration pathway and is involved in homocysteine metabolism and hydrogen sulfide (H2S) formation. Polymorphism of CBS may alter CBS activity and subsequently homocysteine and H2S levels. CBS genostatus with decreased CBS activity has been associated with delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH) [1]. The impact of CBS polymorphisms on functional outcome needs to be determined.
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 two academic institutions in the United States from 2012 to 2015. Common CBS polymorphisms [844ins68 CBS insertion polymorphism W -> I, CBS 699 G -> A (C -> T) single nucleotide polymorphism (SNP) (rs234706), and CBS 1080 C -> T SNP (rs1801181)] were detected using 5’exonnuclease (Taqman) genotyping assays. Analysis of associations between CBS polymorphisms and aSAH was performed. A modified Rankin scale (mRS) score of 3 – 6 were considered as unfavorable outcome.
Results: Samples from 149 aSAH patients were available for analysis. Multivariate analysis included Hunt and Hess grade, modified Fisher grade, Hijdra grade, location, time to treatment and complications. The GG genotype of rs234706 was associated with an unfavorable outcome at discharge (16 ± 11 days; odds ratio = 5.295, p = 0.007) and last follow-up (250 ± 188 days; odds ratio = 3.008, p = 0.015).
Conclusions: The wildtyp GG genotype of rs234706 was independently associated with a poor outcome following. This wildtyp had also been associated to an increased risk for delayed cerebral ischemia in another clinical study. A potential explanation is that the wildtyp genotype results into a decreased CBS activity compared to patients harboring the SNP.
References
- 1.
- Grobelny BT, Ducruet AF, DeRosa PA, Kotchetkov IS, Zacharia BE, Hickman ZL, Fernandez L, Narula R, Claassen J, Lee K, Badjatia N, Mayer SA, Connolly ES Jr. Gain-of-function polymorphisms of cystathionine ß-synthase and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2011 Jul;115(1):101-7.DOI: 10.3171/2011.2.JNS101414
