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 SNPs 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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06072008-160156 |
| Date | 24 July 2008 |
| Creators | Gallek, Matthew J |
| Contributors | Richard A Henker, Jeffrey Balzer, Dianxu Ren, Yvette P. Conley, Sheila A Alexander |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06072008-160156/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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