Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension
Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension
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DOI：
10.1139/y08-045
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发表时间：
2008-08-01
影响因子：
2.1
通讯作者：
Benigni, Ariela
中科院分区：
文献类型：
--
作者：
Caprioli, Jessica;Mele, Caterina;Benigni, Ariela
近50%的高血压患者在盐消耗或盐补充后表现出血压变化，被称为“盐敏感”（SS）。内皮素（ET）系统和肾素-血管紧张素-醛固酮系统（RAAS）活性减弱已被报道为盐敏感性的可能机制。有数据表明，内皮素受体B亚型（ETBR）缺乏的大鼠在高盐饮食中会发生盐敏感性高血压。ETBR基因（EDNRB）是否与人类盐敏感性高血压的遗传易感性有关，目前还没有研究。我们在104例高血压患者（49例盐敏感，55例盐耐药）和110例正常对照中筛选了EDNRB。无新的序列变异，但共同多态性G1065A基因型分布显示，AA + GA基因型在耐盐个体中出现的频率显著高于盐敏感个体（p = 0.007），提示a等位基因具有保护作用。我们还筛选了血管紧张素原基因AGTM235T和血管紧张素转换酶插入/缺失多态性ACE I/D，发现TT基因型与高血压之间存在关联。EDNRB GG与ACE DD/ID基因型联合使用可能对盐敏感性高血压有协同作用。总之，我们的数据证实了ET系统和RAAS在盐敏感性高血压中的作用。
Almost 50% of hypertensive individuals manifest blood pressure changes in response to salt depletion or repletion and are termed "salt sensitive" (SS). Blunted activity of the endothelin (ET) system and the renin-arigiotensin-aldosterone system (RAAS) have been reported as possible mechanisms contributing to salt sensitivity. Data are available that endothelin receptor subtype B (ETBR)-deficient rats develop salt-sensitive hypertension when fed a high-salt diet. Whether the ETBR gene (EDNRB) is involved in genetic predisposition to human salt-sensitive hypertension has not been studied so far. We screened EDNRB in 104 hypertensive patients (49 salt sensitive and 55 salt resistant) and 110 normotensive controls. No new sequence variation was found, but genotype distribution of the common polymorphism G1065A revealed that the AA + GA genotypes were significantly more frequent in salt-resistant than in salt-sensitive individuals (p = 0.007), suggesting a protective role for the A allele. We also screened angiotensinogen gene AGTM235T and angiotensin-converting enzyme insertion/deletion polymorphism ACE I/D and found an association between TT genotype and hypertension. A possible synergistic effect to salt-sensitive hypertension was found by combining EDNRB GG with ACE DD/ID genotypes. In conclusion, our data confirm the role of ET system and RAAS in salt-sensitive hypertension.