Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage
Endothelial nitric oxide synthase polymorphism (-786T→C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage
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DOI：
10.1161/strokeaha.107.496596
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发表时间：
2008-04-01
期刊：
影响因子：
8.3
通讯作者：
Young, William L.
中科院分区：
文献类型：
--
作者：
Ko, Nerissa U.;Rajendran, Pam;Young, William L.
背景和目的：蛛网膜下腔出血（SAH）后的血管痉挛仍然是动脉瘤破裂后死亡和残疾的主要原因。一氧化氮（NO）的可用性降低可能是其发病机制的关键。我们假设，内皮型一氧化氮合酶（eNOS）多态性可能决定血管痉挛在SAH patients.Methods的易感性，我们进行了一项前瞻性队列研究SAH患者和脑血管造影确定血管痉挛。我们对eNOS的3种多态性进行了基因分型：内含子4可变数目串联重复序列，启动子单核苷酸多态性（-786 T-> C SNP）和外显子7编码SNP（894 G-> T编码E298 D）。使用多变量逻辑回归，我们量化了脑血管造影证实的血管痉挛患者中eNOS多态性的相关性。结果-对于eNOS启动子-786 T-> C SNP，CC基因型的存在与任何T基因型相比（CT或TT）与血管痉挛的几率增加相关（比值比= 2.97，95% CI = 1.32至6.67，P = 0.008）。eNOS 894 G-> T或可变数目串联重复多态性与血管痉挛无相关性。结论-这些研究结果表明，影响NO调节的遗传变异有助于SAH患者血管造影性血管痉挛的风险。启动子SNP（-786T -> C）的特异性作用可能决定了该途径调节的NO的作用，这与其他已知的eNOS多态性不同。
Background and Purpose - Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients.Methods - We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (- 786T -> C SNP), and a coding SNP in exon 7 (894G -> T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography.Results - For the eNOS promoter -786T -> C SNP, the presence of the CC genotype compared with any T genotype (CT or TT) was associated with increased odds of vasospasm (odds ratio = 2.97, 95% CI = 1.32 to 6.67, P = 0.008). No association with vasospasm was observed for the eNOS 894G -> T or variable-number tandem-repeat polymorphisms.Conclusions - These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (-786T -> C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.