Associations of Endothelin Polymorphisms and Aneurysm Size at Time of Rupture.
OBJECTIVE
Aneurysm size is an important risk factor for aneurysm rupture. The pathophysiologic mechanisms underlying aneurysm growth remain poorly understood. Endothelin signaling is critical for cerebrovascular blood flow regulation. The influence of endothelin single nucleotide polymorphisms (SNPs) on aneurysm size at the time of rupture has not been previously investigated.


METHODS
Eight common endothelin SNPs were assessed using blood samples from aneurysmal subarachnoid hemorrhage (aSAH) patients enrolled in the Cerebral Aneurysm Renin Angiotensin System study, a prospective, 2-center study that enrolled aSAH patients and controls in the United States from 2012-2015. Genetic evaluation was performed using 5'exonnuclease (Taqman) genotyping assays. Associations of endothelin SNPs and aneurysm size were analyzed.


RESULTS
One-hundred and forty-nine blood samples from aSAH patients were available for analysis. There was a dominant effect of the G allele of the endothelin receptor type A (EDNRA) SNP rs5335 on aneurysm size ≥7 mm (odds ratio = 2.740, 95% confidence interval 1.039-7.228, P = 0.042) along with associations with race and presence of additional aneurysms. The other endothelin SNPs were not associated with aneurysm size.


CONCLUSIONS
The EDNRA SNP rs5335 was independently associated with aneurysms ≥7 mm in size at the time of rupture. Patients with cerebral aneurysms also carrying the G allele of EDNRA SNP rs5335 may develop larger aneurysms before rupture.
Department of Neurosurgery, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg/Saar, Germany. Electronic address: hendrix.philipp@gmail.com.
Philipp
P
Hendrix
Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
Paul M
PM
Foreman
Department of Neurosurgery/Radiology, University of Miami, Florida, USA.
Robert M
RM
Starke
Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
Mark R
MR
Harrigan
Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
Winfield S
WS
Fisher
Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA.
Nilesh A
NA
Vyas
Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA.
Robert H
RH
Lipsky
Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA.
Minkuan
M
Lin
Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA; Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA.
Beverly C
BC
Walters
Seattle Science Foundation, Seattle, Washington, USA.
R Shane
RS
Tubbs
Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Mohammadali M
MM
Shoja
Department of Anesthesiology, University of Miami, Florida, USA.
Jean-Francois
JF
Pittet
Department of Anesthesiology, University of Miami, Florida, USA.
Mali
M
Mathru
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Department of Neurosurgery, Geisinger Health System, Danville, Pennsylvania, USA.
Christoph J
CJ
Griessenauer
D000328:Adult; D000368:Aged; D017542:Aneurysm, Ruptured / Q000000981:diagnostic imaging / Q000235:genetics*; D016232:Endothelins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D015898:Tomography Scanners, X-Ray Computed; D014481:United States
D016232:Endothelins
Aneurysm size; Endothelin; Polymorphism; Subarachnoid hemorrhage