Glutamate-cysteine ligase polymorphism, hypertension, and male sex are associated with cardiovascular events. Biochemical and genetic characterization of Italian subpopulation
Glutamate-cysteine ligase polymorphism, hypertension, and male sex are associated with cardiovascular events. Biochemical and genetic characterization of Italian subpopulation
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DOI：
10.1016/j.ahj.2007.07.029
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Parodi, Oberdan
中科院分区：
文献类型：
--
作者：
Campolo, Jonica;Penco, Silvana;Parodi, Oberdan
背景谷胱甘肽（GSH）是一种重要的血管内清除剂，可保护内皮细胞免受动脉粥样硬化的损伤。然而，目前尚不清楚心血管（CV）事件是否与代谢和遗传因素有关，与意大利亚群的GSH合成有关，以及催化亚基（GCLC）内的谷氨酸-半胱氨酸连接酶多态性是否会影响血液和血浆GSH浓度。（GSH，同型半胱氨酸，半胱氨酸，半胱氨酰甘氨酸），抗氧化维生素（α-生育酚和抗坏血酸），丙二醛，脂质过氧化产物，和GCLC-129 C/T多态性的存在;甲硫氨酸诱导的刺激转硫途径后的实验性高同型半胱氨酸血症在91%的入组受试者中进行。临床、生化和遗传变量与心血管事件（心肌梗死、短暂性脑缺血发作和卒中）的发生相关。结果经多元Logistic回归分析，男性（P = 0.027）、高血压（P = 0.001）和GCLC C/T基因型（P = 0.009）是与事件相关的唯一变量。与野生型相比，T等位基因受试者甲硫氨酸后血浆α-生育酚含量降低（时间x组相互作用P = 0.001）。血浆还原型GSH水平在两个时间点C/T高于C/C基因型受试者（P组= 0.03），而细胞内GSH浓度在基线或postmethion.Conclusions两个基因型组之间没有差异GCLC T等位基因，与高血压和男性，是与CV事件在我们的研究人群。此外，在刺激转硫作用后，细胞内GSH含量在T等位基因受试者中得以保留，这可能是由于GSH周转和输出的增加以及α-生育酚的消耗。
Background Glutathione (GSH) is an important intravascular scavenger that protects endothelial cells from atherosclerosis. However, it is still unknown whether cardiovascular (CV) events are associated with metabolic and genetic factors, linked to GSH synthesis in an Italian subpopulation, and if a glutamate-cysteine ligase polymorphism within the catalytic subunit (GCLC) could affect blood and plasma GSH concentrations.Methods One hundred subjects, with or without CV risk factors, were enrolled to evaluate plasma and erythrocyte redox status (GSH, homocysteine, cysteine, cysteinylglycine), antioxidant vitamins (a-tocopherol and ascorbate), malondialdehyde, a lipid peroxidation product, and the presence of the GCLC-129 C/T polymorphism; an experimental hyperhomocysteinemia after methionine-induced stimulation of transsulfuration pathway was performed in 91% of enrolled subjects. Clinical, biochemical, and genetic variables were correlated with the presence of CV events (myocardial infarction, transient ischemic attacks, and stroke).Results By multiple logistic regression analysis, male sex (P = .027), hypertension (P = .001), and GCLC C/T genotype (P = .009) were the only variables associated with events. Plasma a-tocopherol content decreased postmethionine in the T allele subjects compared with wild type (P for time x group interaction = .001). Plasma-reduced GSH level was higher in C/T than in C/C genotype subjects at both time points (P for group = .03), whereas intracellular GSH concentration did not differ between the 2 genotype groups either at baseline or postmethionine.Conclusions GCLC T allele, together with hypertension and male sex, is associated with CV events in our study population. Moreover, after stimulation of transsulfuration, intracellular GSH content is preserved in T allele subjects, probably by increases in GSH turnover and export, and consumption of a-tocopherol.