ENDOTHELIN POLYMORPHISMS AND OUTCOMES FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE

2.50
Hdl Handle:
http://hdl.handle.net/10755/157504
Type:
Presentation
Title:
ENDOTHELIN POLYMORPHISMS AND OUTCOMES FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE
Abstract:
ENDOTHELIN POLYMORPHISMS AND OUTCOMES FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE
Conference Sponsor:Western Institute of Nursing
Conference Year:2010
Author:Gallek, Mathew, PhD, RN
P.I. Institution Name:University of Arizona
Title:Assistant Professor
Contact Address:1305 N Martin, Tucson, AZ, 85721, USA
INTRODUCTION: Cerebral Vasospasm (CV) is a major contributor to ischemia and poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH); little is known regarding its etiology. It has been suggested that endothelin-1 (ET-1), a potent vasoconstrictor, is related to the formation of CV. Genetic variations of ET-1, the ETA receptor, or the ETB receptor may influence the occurrence of CV and long term outcomes.

PURPOSE: The purpose of this study was to investigate ET-1, the ETA receptor, and the ETB receptor tagging SNPs and their relationship to CV and to long term outcomes.

METHODS: Subjects (N=96), were prospectively recruited for an on-going NIH funded study [100% Caucasian; 76% female (n=73)]. The inclusion criteria were patients age 18-75, with a diagnosis of aneurysmal SAH (Fisher grade ?2), and access to DNA. Persons with a history of a neurologic disease were excluded. Presence/absence of CV was determined by cerebral angiogram independently read by a neurosurgeon. Genotyping of the tagging SNPs was performed using an ABI Prism« 7000 Sequence Detection System and TaqMan« assays. This is a highly automated, high throughput genotyping method for SNPÆs. Modified Rankin Score (MRS) was collected at 6 months post aneurysm rupture. These scores were collected by a trained neuropsychological technician. Graphic analysis, descriptive statistics, and logistic regression were used to analyze relationships.

RESULTS: Of the 96 subjects, and 44 developed CV within 14 days. Of the SNPs that were investigated, RS2070699 showed a significant relationship with CV (p=0.012). 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 other SNPs showed significant relationships with CV or MRS.
CONCLUSION: By investigating all of the tagging SNPs involved with ET-1, the ETA receptor, and the ETB receptor the majority of the genetic variation within the ET-1 gene is accounted for in this analysis. The variant allele of RS2070699 is associated with CV. A subject with a heterozygous genotype was 2.97 times more likely to have CV when compared to a subject with a homozygous wild type genotype. While a subject with the homozygous variant genotype was at the highest risk of have CV. These subjects were 8.36 times more likely to have CV when compared to a subject with the homozygous variant genotype. The significant relationship found between this tagging SNP and CV is the first step that may allow clinicians and nurses to screen for SNPs that are associated with the development of CV. This screening will allow clinicians and nurses to focus resources on patients with increased risk of CV and worse outcomes.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleENDOTHELIN POLYMORPHISMS AND OUTCOMES FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGEen_GB
dc.identifier.urihttp://hdl.handle.net/10755/157504-
dc.description.abstract<table><tr><td colspan="2" class="item-title">ENDOTHELIN POLYMORPHISMS AND OUTCOMES FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2010</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Gallek, Mathew, PhD, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of Arizona</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Assistant Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">1305 N Martin, Tucson, AZ, 85721, USA</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">mgallek@nursing.arizona.edu</td></tr><tr><td colspan="2" class="item-abstract">INTRODUCTION: Cerebral Vasospasm (CV) is a major contributor to ischemia and poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH); little is known regarding its etiology. It has been suggested that endothelin-1 (ET-1), a potent vasoconstrictor, is related to the formation of CV. Genetic variations of ET-1, the ETA receptor, or the ETB receptor may influence the occurrence of CV and long term outcomes.<br/><br/>PURPOSE: The purpose of this study was to investigate ET-1, the ETA receptor, and the ETB receptor tagging SNPs and their relationship to CV and to long term outcomes. <br/><br/>METHODS: Subjects (N=96), were prospectively recruited for an on-going NIH funded study [100% Caucasian; 76% female (n=73)]. The inclusion criteria were patients age 18-75, with a diagnosis of aneurysmal SAH (Fisher grade ?2), and access to DNA. Persons with a history of a neurologic disease were excluded. Presence/absence of CV was determined by cerebral angiogram independently read by a neurosurgeon. Genotyping of the tagging SNPs was performed using an ABI Prism&laquo; 7000 Sequence Detection System and TaqMan&laquo; assays. This is a highly automated, high throughput genotyping method for SNP&AElig;s. Modified Rankin Score (MRS) was collected at 6 months post aneurysm rupture. These scores were collected by a trained neuropsychological technician. Graphic analysis, descriptive statistics, and logistic regression were used to analyze relationships. <br/><br/>RESULTS: Of the 96 subjects, and 44 developed CV within 14 days. Of the SNPs that were investigated, RS2070699 showed a significant relationship with CV (p=0.012). 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 other SNPs showed significant relationships with CV or MRS. <br/>CONCLUSION: By investigating all of the tagging SNPs involved with ET-1, the ETA receptor, and the ETB receptor the majority of the genetic variation within the ET-1 gene is accounted for in this analysis. The variant allele of RS2070699 is associated with CV. A subject with a heterozygous genotype was 2.97 times more likely to have CV when compared to a subject with a homozygous wild type genotype. While a subject with the homozygous variant genotype was at the highest risk of have CV. These subjects were 8.36 times more likely to have CV when compared to a subject with the homozygous variant genotype. The significant relationship found between this tagging SNP and CV is the first step that may allow clinicians and nurses to screen for SNPs that are associated with the development of CV. This screening will allow clinicians and nurses to focus resources on patients with increased risk of CV and worse outcomes.<br/></td></tr></table>en_GB
dc.date.available2011-10-26T19:55:58Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T19:55:58Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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