The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension
The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension
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DOI：
10.1097/01.hjh.0000234110.54110.56
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发表时间：
2006-07-01
影响因子：
4.9
通讯作者：
Zalba, Guillermo
中科院分区：
文献类型：
--
作者：
Moreno, Maria U.;San Jose, Gorka;Zalba, Guillermo
目的氧化应激参与高血压的发生。还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是吞噬细胞和血管细胞中超氧化物的主要来源。CYBA（编码p22 phox的人类基因）的C242 T多态性已被发现与动脉粥样硬化患者的血管NADPH氧化酶活性在功能上相关。我们研究了C242 T多态性与高血压的相关性及其对NADPH氧化酶活性的潜在影响。方法采用病例对照研究方法，随机抽取326例高血压患者和297例正常血压对照者作为研究对象，采用限制性片段长度多态性（RFLP）或等位基因判别法检测CYBA基因多态性，分析CYBA基因C242 T多态性与CYBA基因-930A/G多态性的相互作用。结果高血压组CC基因型和C等位基因频率均显著高于正常血压组（P < 0.05）;在logistic回归分析中校正潜在混杂因素后，CC基因型仍与高血压相关。CC组吞噬细胞NADPH氧化酶活性明显高于CT组和TT组（P < 0.05）。CC型高血压患者血浆von Willebrand因子水平明显高于TT型高血压患者（P < 0.05）。CYBA基因C242 T多态性与CYBA基因启动子区-930A/G多态性不存在连锁不平衡，CYBA基因启动子区-930A/G多态性与高血压相关。此外，高血压携带CC基因型的多态性表现出NADPH氧化酶介导的氧化应激和内皮损伤的功能。
Objective Oxidative stress is implicated in hypertension. The reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main source of superoxide in phagocytic and vascular cells. The C242T polymorphism of CYBA, the human gene that encodes p22phox, has been found to be functionally associated with vascular NADPH oxidase activity in atherosclerotic patients. We investigated the association of the C242T polymorphism with hypertension and its potential impact on NADPH oxidase activity. We also analysed the interaction of C242T polymorphism with the -930A/G CYBA variant.Design Case-control study in a random sample of 623 subjects ( 326 hypertensive patients and 297 normotensive controls) from the general population.Methods CYBA polymorphisms were determined by restriction fragment length polymorphism (RFLP) or allelic discrimination. NADPH oxidase activity and p22phox expression were quantified in phagocytic cells by chemiluminescence and by northern and western blots, respectively.Results The prevalence of the CC genotype and the C allele frequency were significantly higher (P < 0.05) in hypertensives than in normotensives. CC genotype remained associated with hypertension after adjusting for potential confounders in a logistic regression analysis. Increased phagocytic NADPH oxidase activity was observed in CC hypertensives compared with CT and TT hypertensives (P < 0.05). Enhanced plasma levels of von Willebrand factor were found in CC hypertensives compared with TT hypertensives (P < 0.05). The C242T polymorphism was not in linkage disequilibrium with the -930A/G CYBA promoter variation, which also associates with hypertension.Conclusion The C242T CYBA polymorphism is associated with essential hypertension. Furthermore, hypertensives carrying the CC genotype of this polymorphism exhibit features of NADPH oxidase-mediated oxidative stress and endothelial damage.