血管扩张素II-1型受体基因多态性与高血压及血浆NO、ET关系的研究

Investigation of relationship between gene polymorphism of angiotensin II type 1 receptor and plasma nitric oxide and endothelin in essentital hypertension

目的研究血管紧张素II-1型受体(AngiogenesisIIType1Receptor,AT1R)基因1166位点多态性与原发性高血压(EssentialHypertension,EH)的关系和血浆一氧化氮(NitricOxide,NO)、内皮素(Endothelin,ET)在EH发病中的相关性。方法采用聚合酶链反应、限制性内切酶酶解及电泳分型的方法对AT1R基因1166位点的多态性进行分析,硝酸还原酶法和放射免疫法分别测定两组血浆NO、ET值。结果①EH组中1166C等位基因频率显著高于对照组(P<0.05)。②EH组与对照组比较NO活性降低;ET水平升高(P<0.001)。③EH组中CC型血浆NO水平明显低于AC型(P<0.01);血浆NO、ET水平在AA、AC型之间无显著性差异(P<0.05)。结论①AT1R基因1166位点多态性与EH相关,1166C等位基因是EH发病的危险因素。②EH组存在血管内皮舒缩功能障碍,表现为血浆NO浓度降低、ET浓度升高。③EH血管内皮功能障碍与AT1R基因A1166C多态性有关,1166CC基因型可导致血管内皮舒缩功能障碍,提示EH血管内皮功能障碍可能存在遗传机制。④血浆NO水平与EH发病危险呈负相关;而血浆ET浓度升高是EH发病的危险因素。

Objective To investigate Angiotensin II Type 1 Receptor （ATIR） Gene Polymorphism and its relationship with plasma Nitric Oxide（NO） and Engothelin（ET）in Essential Hypertension. Methods Gene polymorphism of ATIR at site 1166 was detected with polymerase chain reaction （PCR）, digestion of restriction enzyme and electrophoresis. Plasma NO and ET activities were measured by deoxidized nitric acid and Radioimmunoassay Kit, Result ① The frequency of ATIR 1166C allele was significantly higher in essential hypertension group than in control group （P〈0,05）, ②There was lower activity of plasma NO in essential hypertension group while highter activity of plasma ET in essential hypertension group （P〈0.01）, ③The plasma NO level of 1166CC genotype was significantly lower than that of 1166AC （P〈0.01）. Conclusions ①There was relationship between ATIR gene polyorphism and the pathogenesis of essential hypertension. The 1166C allele may be dangerous genetic factor involved in the occurrence of EH. ②There was dysfunctionof relaxation and contraction in endothelium： lower activity of plasma NO and highter activity of plasma ET in EH. ③There was relationship between the function of endothelium and ATIR gene polymorphism, 1166CC genotype could cause the dysfunction of relaxation or contraction.④The high concentration of plasma NO decreases the danger of EH while ET increases the danger of EH.