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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. |
