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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

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 (Unpublished)

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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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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gallek, Matthew Jgallekmj@upmc.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHenker, Richard Arhe001@pitt.eduRHE001
Committee MemberRen, Dianxudir8@pitt.eduDIR8
Committee MemberBalzer, Jeffreybalzerjr@upmc.edu
Committee MemberAlexander, Sheila Asalexand@pitt.eduSALEXAND
Committee MemberConley, Yvette Pyconley@pitt.eduYCONLEY
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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