血管紧张素原基因多态性与高血压血尿醛固酮水平相关

目的研究血管紧张素原(Angiotensinogen,AGT)基冈5个单核苷酸多态性(single nucleotide polymorphisms,SNPs)及其构成的单倍型在中国汉族人群中与原发性高血压的相关性及各SNP与高血压患者血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)、血浆和尿醛固酮(Ald)水平的关系。方法采用MassARRAYTM系统质谱检测技术,在500例原发性高血压患者和500名正常对照者中,对AGT基因启动子区域的C-532T、A-20C、G-6A及编码区的T174M和M235T进行基因分型。用放免法检测高血压患者PRA、AngⅡ、血尿Ald水平。结果5种SNP的等位基因频率和单倍型分布在原发性高血压组和对照组中均无显著差异(P>0．05);男性高血压患者中C-532T多态CT TT基因型个体尿Ald水平显著高于CC型个体(6．52 vs 5．19μg／d,P=0．03);女性高血压患者G-6A多态GG GA基因型个体血Ald水平显著高于AA型个体(78．63 vs 58．86 pg/ml,P=0．015);女性高血压患者M235T多态MM MT基因型个体血Ald水平显著高于TT型个体(78．73 vs 58．81 pg／ml,P=0．03); A-20C多态AC CC基因型与G-6A多态GG GA基因型联合者尿Ald水平(P<0．05)、体重指数(P <0．01)显著高于其他联合基因型。结论AGT基因5个SNP及单倍型分布在高血压患者和正常血压对照之间无显著差异,AGT基因的SNP分布与原发性高血压患者血尿醛固酮水平有关。

Polymorphisms of Angiotensinogen Gene are Associated with Plasma and Uric Aldosterone Level in Essential Hypertensive Patients

Objective To investigate the relationship between 5 single nucleotide polymorphisms (SNPs) and its haplotype of angiotensinogen (AGT) gene and essential hypertension in a Chinese population, as well as to determine whether the SNPs are associated with plasma renin activity ( PRA) , plasma angiotensin II (AngII) , plasma and uric aldosterone level in essential hypertensives. Methods Genotyping for 5 SNPs (C-532T, A-20C, G-6A, T174M, M235T) of AGT gene was performed through MALDI-TOF technology using MassARRAYTM System in 500 essential hypertensives and 500 normal controls. Radioimmunoassay was applied to measure PRA, plasma Angll level, plasma and uric aldosterone level in hypertensives. Results No significant difference of distribution of each SNP and haplotype of AGT gene was observed between essential hypertensives and normal controls. SNPs of AGT gene were found to be associated with plasma or uric aldosterone level in hypertensives. These relationships were present in male patients carrying T-532 and uric aldosterone level, as well as female patients with G-6 or M235 and plasma aldosterone level. The hypertensives carrying both C-20 and G-6 were found to be associated with higher body mass index and uric aldosterone level. Conclusion The distribution of 5 SNPs or hyplotype of AGT gene was not associated with essential hypertension but associated with plasma and uric aldosterone level in essential hypertensives.