Gallek, Matthew J
(2008)
ENDOTHELIN-1 POLYMORPHISMS AND ENDOTHELIN-1 CEREBROSPINAL FLUID PROTEIN EXPRESSION AND THEIR RELATIONSHIPS TO CEREBRAL VASOSPASM AND LONG TERM OUTCOMES IN INDIVIDUALS FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease that affects approximately 25,000 people a year in the United States. Cerebral vasospasm (CV) is a common complication after SAH. In addition SAH patients have poor long term outcomes, with 40-50% of patients suffering severe neurological disabilities. The most vital step in preventing CV and poor long term outcomes is identifying patients at increased risk of these poor outcomes. Endothelin-1 (ET-1) is a potent vasoconstrictor that may play a role in the pathogenesis of CV. Genetic variation within the ET-1 gene may also account for some of the variance observed in the outcomes of SAH patients. The purpose of this study was to examine the effects of ET-1 CSF protein expression, and ET-1 SNPs on CV in individuals suffering from SAH. In addition, the relationship between long-term outcomes, ET-1 SNPs, and ET-1 CSF protein expression in patients with SAH was evaluated. This study included individuals ages 18-75 with a diagnosis of aneurysmal SAH. CSF samples were collected from a drainage catheter. ET-1 levels CSF were measured using chemiluminescent ELISA kits. Genotyping was performed using TaqMan® allele discrimination assays. Individuals with CV had average CSF ET-1 elimination rates (7.94±6.47pg/hr) that were increased in the 72 hours before angiography when compared to individuals without CV (4.35±3.02 pg/hr). Of the 9 ET-1 SNP's investigated, the variant allele of 1 SNP (rs2070699) was associated with the development of CV. The odds ratio of the heterozygous genotype compared to the homozygous wild-type genotype was 2.970 with a 95% confidence interval of 0.998 to 8.836. The odds ratio for the homozygous variant genotype compared to the homozygous wild-type genotype was 8.356 with a 95% confidence interval of 2.032 to 34.371. No relationships were found between ET-1 SNPs and long-term outcomes. In addition a predictive model with CSF ET-1 levels and ET-1 SNPs had no significant relationships with long-term outcomes. This study supports the use of ET-1 levels and ET-1 genotypes as predictors of CV, but not of long term outcomes.
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| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
24 July 2008 |
| Date Type: |
Completion |
| Defense Date: |
16 May 2008 |
| Approval Date: |
24 July 2008 |
| Submission Date: |
7 June 2008 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Nursing > Nursing |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Cerebral Vasospasm; Endothelin-1; Genetic Polymorphisms; Subarachnoid Hemorrhage |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-06072008-160156/, etd-06072008-160156 |
| Date Deposited: |
10 Nov 2011 19:46 |
| Last Modified: |
15 Nov 2016 13:44 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8029 |
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