Hendrix Philipp, Foreman Paul M, Harrigan Mark R, Fisher Winfield S, Vyas Nilesh A, Lipsky Robert H, Lin Minkuan, Walters Beverly C, Tubbs R Shane, Shoja Mohammadali M, Pittet Jean-Francois, Mathru Mali, Griessenauer Christoph J
Department of Neurosurgery, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg/Saar, Germany.
Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
World Neurosurg. 2017 May;101:514-519. doi: 10.1016/j.wneu.2017.02.062. Epub 2017 Feb 22.
Nitric oxide is critical in the regulation of cerebral blood flow and smooth muscle proliferation. It is synthesized by 3 nitric oxide synthase (NOS) isoforms: neuronal, inducible, and endothelial NOS (eNOS). Aneurysmal subarachnoid hemorrhage (aSAH) causes endothelial dysfunction that, in turn, contributes to pathophysiologic processes surrounding aSAH. Previous studies reported an association of an eNOS single nucleotide polymorphism (SNP) with the clinical sequelae of aSAH. Here, we further elucidate the impact of this eNOS SNP on the clinical course after aSAH.
The Cerebral Aneurysm Renin Angiotensin System study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012-2015. Blood samples from all patients enrolled in the study were used for genetic evaluation using 5'exonuclease (Taqman) genotyping assays. Associations between the eNOS SNP rs2070744 (786 T->C) and clinical course after aSAH were analyzed.
Samples from 149 aSAH patients were available for analysis. The C allele of the eNOS SNP independently predicted an increased risk for delayed cerebral ischemia (OR = 2.936, 95% CI 1.048-8.226, P = 0.040). The eNOS SNP rs2070744 was not associated with functional outcome or size of aneurysm at the time of rupture.
The present study is the first to demonstrate that the C allele of the eNOS SNP 786 T->C rs2070744 is independently associated with an increased risk for delayed cerebral ischemia following aSAH.
一氧化氮在脑血流调节和平滑肌增殖中起关键作用。它由3种一氧化氮合酶（NOS）亚型合成：神经元型、诱导型和内皮型NOS（eNOS）。动脉瘤性蛛网膜下腔出血（aSAH）会导致内皮功能障碍，进而促成围绕aSAH的病理生理过程。既往研究报道eNOS单核苷酸多态性（SNP）与aSAH的临床后遗症有关。在此，我们进一步阐明这种eNOS SNP对aSAH后临床病程的影响。
脑动脉瘤肾素血管紧张素系统研究于2012年至2015年在美国的2家学术机构前瞻性纳入aSAH患者。研究中纳入的所有患者的血样用于采用5'外切核酸酶（Taqman）基因分型检测进行基因评估。分析eNOS SNP rs2070744（786 T→C）与aSAH后临床病程之间的关联。
有149例aSAH患者的样本可供分析。eNOS SNP的C等位基因独立预测延迟性脑缺血风险增加（OR = 2.936，95% CI 1.048 - 8.226，P = 0.040）。eNOS SNP rs2070744与破裂时的功能结局或动脉瘤大小无关。
本研究首次证明eNOS SNP 786 T→C rs207
