Department of Neurosurgery, New York University Medical Center, New York, New York, USA.
J Neurosurg. 2011 Jul;115(1):101-7. doi: 10.3171/2011.2.JNS101414. Epub 2011 Mar 18.
Cystathionine β-synthase (CBS) is an enzyme that metabolizes homocysteine to form H(2)S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H(2)S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH).
Patients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C→T, 844ins68, and 1080C→T) by polymerase chain reaction. Serum homocysteine levels (μmol/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI.
There were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT/ins genotypes were less likely to experience DCI relative to those with the 844 WT/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis.
Polymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H(2)S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.
胱硫醚β-合酶（CBS）是一种在大脑中将同型半胱氨酸代谢为 H₂S 的酶。硫化氢作为一种血管扩张剂以及神经元离子通道和多种细胞内信号通路的调节剂发挥作用。鉴于 H₂S 的众多影响，作者假设 CBS 基因具有功能获得性多态性的患者在蛛网膜下腔出血（aSAH）后会经历延迟性脑缺血（DCI）发生率降低。
患者被纳入前瞻性观察性 aSAH 结局数据库。从口腔拭子中提取 DNA，并通过聚合酶链反应对 CBS 基因的 3 个功能多态性（699C→T、844ins68 和 1080C→T）进行测序。测定血清同型半胱氨酸水平（μmol/L）。采用多变量分析确定 CBS 基因型与血管痉挛和 DCI 发生之间的关系。
本研究共纳入 87 例患者。研究中没有发现任何多态性与血管痉挛的发生率显著相关。然而，在控制入院高血压后，与 844 WT/WT 基因型相比，具有功能获得性 844 WT/ins 基因型的患者发生 DCI 的可能性较低（86 例患者，p = 0.050），而功能降低基因型 1080 TT 发生 DCI 的可能性高于 1080 CC 和 CT 基因型（84 例患者，p = 0.042）。在本分析中，血清同型半胱氨酸水平与血管痉挛或 DCI 的严重程度均无相关性。
赋予功能获得性的 CBS 基因多态性可能与 aSAH 后 DCI 风险降低相关，与血清同型半胱氨酸无关。H₂S 信号传导可能通过不涉及大血管扩张的机制介导对 aSAH 后 DCI 的保护作用。
