Associations of Endothelin Polymorphisms and Aneurysm Size at Time of Rupture.
BACKGROUND AND PURPOSE
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.
['Hendrix|Philipp|P|', 'Foreman|Paul M|PM|', 'Starke|Robert M|RM|', 'Harrigan|Mark R|MR|', 'Fisher|Winfield S|WS|', 'Vyas|Nilesh A|NA|', 'Lipsky|Robert H|RH|', 'Lin|Minkuan|M|', 'Walters|Beverly C|BC|', 'Tubbs|R Shane|RS|', 'Shoja|Mohammadali M|MM|', 'Pittet|Jean-Francois|JF|', 'Mathru|Mali|M|', 'Griessenauer|Christoph J|CJ|']
D000328:Adult D000368:Aged D017542:Aneurysm, Ruptured D016232:Endothelins D005260:Female D020022:Genetic Predisposition to Disease D006801:Humans D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D012189:Retrospective Studies D012307:Risk Factors D015898:Tomography Scanners, X-Ray Computed D014481:United States
Endothelin Polymorphism Aneurysm size Subarachnoid hemorrhage