Neurology Section, Internal Medicine Department, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
Clin Chim Acta. 2010 Jun 3;411(11-12):840-5. doi: 10.1016/j.cca.2010.02.071. Epub 2010 Mar 1.
Gamma-glutamyl carboxylation, a reaction essential for the biosynthesis of vitamin K-dependent coagulation factors, requires the participation of the gamma-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKORC1), and NAD(P)H:quinone oxidoreductase (NQO1). We evaluated the role of these genotype polymorphisms in patients with large-artery atherosclerotic stroke.
In this hospital-based case-control study, 117 patients who were categorized as having large-artery atherosclerotic stroke and 115 age- and gender-matched controls were recruited. Genotyping determination for the GGCX1 (Gln325Arg), NQO1 (Pro187Ser), and VKORC1 (rs9923231) polymorphisms was performed. The associations of genotype with ischemic stroke (IS) risk were examined.
A higher genotypic frequency of NQO1 C609T was found in the controls than in the patients, manifesting a 0.47-fold risk reduction in IS (95% CI=0.25-0.87). A tendency toward a reduced IS risk was statistically significant in those subjects who carried a greater number of the NQO1, GGCX, and VKORC1 polymorphisms (aOR=0.58, P(trend)=0.005). The synergistic effect of multiple genes on risk reduction was more significant in a subset of patients who were not alcoholics and who were non-smokers (P<0.05).
Compartmentation of coagulation factor metabolism may account for the preferential role of NQO1, GGCX, and VKORC1 polymorphisms to lower the risk for large-artery atherosclerotic stroke.
γ-谷氨酰羧化反应是维生素 K 依赖性凝血因子生物合成所必需的反应，需要γ-谷氨酰羧化酶（GGCX）、维生素 K 环氧化物还原酶（VKORC1）和 NAD（P）H：醌氧化还原酶（NQO1）的参与。我们评估了这些基因型多态性在大动脉粥样硬化性卒中患者中的作用。
在这项基于医院的病例对照研究中，招募了 117 名被归类为大动脉粥样硬化性卒中的患者和 115 名年龄和性别匹配的对照者。对 GGCX1（Gln325Arg）、NQO1（Pro187Ser）和 VKORC1（rs9923231）多态性进行了基因分型测定。检查了基因型与缺血性卒中（IS）风险的相关性。
在对照组中，NQO1 C609T 的基因型频率较高，IS 风险降低了 0.47 倍（95%CI=0.25-0.87）。在携带更多 NQO1、GGCX 和 VKORC1 多态性的受试者中，IS 风险呈降低趋势，具有统计学意义（aOR=0.58，P（趋势）=0.005）。在非酗酒和不吸烟的患者亚组中，多个基因协同作用降低风险的效果更为显著（P<0.05）。
凝血因子代谢的区室化可能解释了 NQO1、GGCX 和 VKORC1 多态性降低大动脉粥样硬化性卒中风险的优先作用。
