Endothelin-1 and endothelin receptor gene variants and their association with negative outcomes following aneurysmal subarachnoid hemorrhage

Biol Res Nurs. 2013 Oct;15(4):390-7. doi: 10.1177/1099800412459674. Epub 2012 Sep 19.

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that affects approximately 30,000 people a year in the United States. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) are common complications after aSAH. In addition, aSAH patients have a high risk of poor long-term outcomes. Endothelin-1 (ET-1), a potent vasoconstrictor, or its two types of receptors, ET receptor A (ETA) and ET receptor B (ETB), may play a role in the pathogenesis of DCI and CV. Genetic variations within the ET-1, ETA, or ETB genes may also account for variance observed in the outcomes of aSAH patients. The purpose of this study was to describe the distribution of the Lys198Asn polymorphism, a known functional SNP in the ET-1 gene, and tagging SNPs of the ET-1, ETA, and ETB genes in individuals recovering from aSAH. This study also investigated the relationships among the ET polymorphisms, DCI, and global functional outcomes measured at 3 and 6 months after aSAH. Participants included individuals aged 18-75 years with a diagnosis of aSAH. There was a trend found between the variant allele of an ET-1 SNP (rs6912834) and angiographic vasospasm. There were also associations found between two ETB SNPs (rs9574124 and rs3027111) and poor outcomes as measured by the Glasgow Outcome scale at 3 months. These findings support the role of ET-1 and ETB in recovery following aSAH.

Keywords: aneurysmal subarachnoid hemorrhage; cerebral vasospasm; delayed cerebral ischemia; endothelin receptor A; endothelin receptor B; endothelin-1; functional outcomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Ischemia / genetics
  • Brain Ischemia / mortality
  • Endothelin-1 / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptor, Endothelin A / genetics*
  • Receptor, Endothelin B / genetics*
  • Risk Factors
  • Subarachnoid Hemorrhage / genetics*
  • Subarachnoid Hemorrhage / mortality*
  • Vasospasm, Intracranial / genetics
  • Vasospasm, Intracranial / mortality
  • Young Adult

Substances

  • Endothelin-1
  • Receptor, Endothelin A
  • Receptor, Endothelin B