Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage
OBJECTIVE Cystathionine β-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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:128 |
|---|---|
| Enthalten in: |
Journal of neurosurgery - 128(2018), 6 vom: 02. Juni, Seite 1771-1777 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hendrix, Philipp [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.09.2019 Date Revised 13.09.2019 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3171/2017.2.JNS162933 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM274509636 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM274509636 | ||
| 003 | DE-627 | ||
| 005 | 20231225003637.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3171/2017.2.JNS162933 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0915.xml |
| 035 | |a (DE-627)NLM274509636 | ||
| 035 | |a (NLM)28777022 | ||
| 035 | |a (PII)2017.2.JNS162933 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hendrix, Philipp |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.09.2019 | ||
| 500 | |a Date Revised 13.09.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE Cystathionine β-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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADC = apparent diffusion coefficient | |
| 650 | 4 | |a CARAS = Cerebral Aneurysm Renin Angiotensin System | |
| 650 | 4 | |a CBS = cystathionine β-synthase | |
| 650 | 4 | |a DCI = delayed cerebral ischemia | |
| 650 | 4 | |a SNP = single nucleotide polymorphism | |
| 650 | 4 | |a aSAH = aneurysmal subarachnoid hemorrhage | |
| 650 | 4 | |a aneurysm | |
| 650 | 4 | |a cystathionine beta-synthase | |
| 650 | 4 | |a mRS = modified Rankin Scale | |
| 650 | 4 | |a outcome | |
| 650 | 4 | |a polymorphism | |
| 650 | 4 | |a subarachnoid hemorrhage | |
| 650 | 4 | |a vascular disorders | |
| 650 | 7 | |a Cystathionine beta-Synthase |2 NLM | |
| 650 | 7 | |a EC 4.2.1.22 |2 NLM | |
| 650 | 7 | |a Hydrogen Sulfide |2 NLM | |
| 650 | 7 | |a YY9FVM7NSN |2 NLM | |
| 700 | 1 | |a Foreman, Paul M |e verfasserin |4 aut | |
| 700 | 1 | |a Harrigan, Mark R |e verfasserin |4 aut | |
| 700 | 1 | |a Fisher, Winfield S |e verfasserin |4 aut | |
| 700 | 1 | |a Vyas, Nilesh A |e verfasserin |4 aut | |
| 700 | 1 | |a Lipsky, Robert H |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Mingkuan |e verfasserin |4 aut | |
| 700 | 1 | |a Walters, Beverly C |e verfasserin |4 aut | |
| 700 | 1 | |a Tubbs, R Shane |e verfasserin |4 aut | |
| 700 | 1 | |a Shoja, Mohammadali M |e verfasserin |4 aut | |
| 700 | 1 | |a Pittet, Jean-Francois |e verfasserin |4 aut | |
| 700 | 1 | |a Mathru, Mali |e verfasserin |4 aut | |
| 700 | 1 | |a Griessenauer, Christoph J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of neurosurgery |d 1945 |g 128(2018), 6 vom: 02. Juni, Seite 1771-1777 |w (DE-627)NLM000006254 |x 1933-0693 |7 nnns |
| 773 | 1 | 8 | |g volume:128 |g year:2018 |g number:6 |g day:02 |g month:06 |g pages:1771-1777 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3171/2017.2.JNS162933 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 128 |j 2018 |e 6 |b 02 |c 06 |h 1771-1777 | ||