Endothelin polymorphisms as a risk factor for cerebral aneurysm rebleeding following aneurysmal subarachnoid hemorrhage

Academic Article


  • Background Aneurysm rebleeding following presentation with aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor functional outcome. While a substantial genetic contribution to aneurysm formation and rupture is known, the genetic influence on the risk of rebleeding is poorly understood. Objective To evaluate the role of common endothelin polymorphisms in aneurysm rebleeding. Patients and methods Blood sample from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The CARAS study prospectively enrolled aSAH patients at two academic institutions in the United States from 2012 to 2015. Common endothelin SNPs were detected using 5′exonnuclease (Taqman) genotyping assays. Analysis of associations between endothelin single nucleotide polymorphisms (SNP) and aneurysm rebleeding was performed. Results One hundred and forty-nine aSAH patients were included. Acute spontaneous aneurysm rebleeding occurred in 5 (3.4%) patients. Multivariable analysis identified the TT genotype for EDN1 G/T SNP (rs2070699; OR 97.4, 95% CI 3.825–2479.984, p = 0.006) as an independent risk factor for aneurysm rebleeding. Aneurysm rebleeding was associated with an unfavorable functional outcome (mRS 3–6) at last follow up in all 5 patients. Conclusion Aneurysm rebleeding following presentation with aSAH was independently associated with the TT genotype of the EDN1 G/T SNP. All patients with acute spontaneous aneurysm rebleeding suffered a poor functional outcome at last follow up.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Foreman PM; Starke RM; Hendrix P; Harrigan MR; Fisher WS; Vyas NA; Lipsky RH; Lin M; Walters BC; Pittet JF
  • Start Page

  • 65
  • End Page

  • 69
  • Volume

  • 157