Skov Karin, Madsen Jens Kristian, Hansen Hans Erik, Zagato Laura, Frandsen Erik, Bianchi Giuseppe, Mulvany Michael John
Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark.
J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):47-55. doi: 10.3317/jraas.2006.006.
INTRODUCTION. The pathogenesis of essential hypertension (EH) has a major genetic component and is associated with renal abnormalities. Normotensive offspring of hypertensive parents are likely to develop EH and are a suitable population for identifying possible relations between genetic and renal abnormalities.
We investigated if renin-angiotensinaldosterone system associated genotypes (angiotensinogen [M235T] and ACE [I/D]) are related to blood pressure (BP), renal haemodynamics and sodium excretion in sex and age-matched (1835 years) healthy Caucasian offspring of either two parents with EH (n=101, EH-offspring) or two normotensive parents (n=50, controls). The alpha-adducin polymorphism (G460W) was also investigated.
Compared to controls, BP, heart rate, renal vascular resistance (RVR) and urinary sodium excretion were, respectively, 5%, 7%, 15% and 20% higher in EHoffspring. In controls, the TT-genotype of the M235T angiotensinogen polymorphism was associated with higher BP and higher plasma angiotensinogen. By contrast, in EHoffspring the TT-genotype was associated with lower BP and unchanged plasma angiotensinogen. Plasma angiotensinogen correlated positively with BP in EH-offspring, with a similar tendency (p=0.08) in controls. The distributions of the three candidate polymorphisms were similar in EH-offspring and controls. There were no associations between any of the polymorphisms and any of the renal parameters measured.
The markedly greater RVR, proportionally larger than the greater BP, supports a role for RVR in the pathogenesis of EH. The lack of association between the candidate polymorphisms and the investigated parameters, even in this homogenous and for hypertension strongly predisposed group, suggests that the polymorphisms investigated do not play important roles in the pathogenesis of hypertension.
引言。原发性高血压（EH）的发病机制有很大的遗传成分，且与肾脏异常有关。高血压父母的血压正常的后代很可能会患EH，是用于确定遗传和肾脏异常之间可能关系的合适人群。
我们研究了肾素 - 血管紧张素 - 醛固酮系统相关基因型（血管紧张素原[M235T]和ACE[I/D]）是否与血压（BP）、肾脏血流动力学以及钠排泄相关，这些研究对象为年龄和性别匹配（18 - 35岁）的健康白种人后代，他们的父母一方或双方患有EH（n = 101，EH后代）或父母双方血压正常（n = 50，对照组）。同时也研究了α - 内收蛋白多态性（G460W）。
与对照组相比，EH后代的血压、心率、肾血管阻力（RVR）和尿钠排泄分别高出5%、7%、15%和20%。在对照组中，血管紧张素原M235T多态性的TT基因型与较高的血压和较高的血浆血管紧张素原相关。相比之下，在EH后代中，TT基因型与较低的血压和不变的血浆血管紧张素原相关。血浆血管紧张素原在EH后代中与血压呈正相关，在对照组中有类似趋势（p = 0.08）。三种候选多态性在EH后代和对照组中的分布相似。所测量的任何一种多态性与任何一种肾脏参数之间均无关联。
明显更大的RVR，与升高的血压相比比例更大，支持RVR在EH发病机制中起作用。候选多态性与所研究参数之间缺乏关联，即使在这个同质且高血压易感性很强的群体中也是如此，这表明所研究的多态性在高血压发病机制中不发挥重要作用。
