title: Endothelin-1 and endothelin receptor gene variants and their association with negative outcomes following aneurysmal subarachnoid hemorrhage.
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.
authors.affiliation: 1University of Arizona, College of Nursing, Tucson, AZ, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gallek
authors.forename: Sheila
authors.initials: S
authors.lastname: Alexander
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Crago
authors.forename: Paula
authors.initials: P
authors.lastname: Sherwood
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: Samuel
authors.initials: S
authors.lastname: Poloyac
authors.forename: Yvette
authors.initials: Y
authors.lastname: Conley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000235:genetics / Q000401:mortality; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044022:Receptor, Endothelin A / Q000235:genetics*; D044023:Receptor, Endothelin B / Q000235:genetics*; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000235:genetics* / Q000401:mortality*; D020301:Vasospasm, Intracranial / Q000235:genetics / Q000401:mortality; D055815:Young Adult
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B