Gene polymorphisms of the renin-angiotension-aldosterone system and the risk of ischemic stroke: a role of the A1166C/AT1 gene variant
Gene polymorphisms of the renin-angiotension-aldosterone system and the risk of ischemic stroke: a role of the A1166C/AT1 gene variant
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DOI：
10.1097/00004872-200411000-00015
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发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Volpe, M
中科院分区：
文献类型：
--
作者：
Rubattu, S;Di Angelantonio, E;Volpe, M
目的 肾素-血管紧张素-醛固酮系统（RAAS）基因对卒中（一种多因素、多基因的心血管特征）易感性的作用仍在研究中。在本研究中，我们表征了 RAAS 基因在人类患缺血性中风的易感性中的贡献作用。方法在撒丁岛（一个地中海大岛，人口种族隔离众所周知）的 215 例病例（仅包括动脉粥样硬化血栓和腔隙性血栓）和 236 名对照人群中，对 RAAS 基因的等位基因和基因型频率进行了表征。在整个人群中进行了统计分析，并且基于血管紧张素 II 受体 (AT1) 基因型与高血压之间的显着相互作用，也在高血压亚组中进行了重复。结果 当假设传播的主导模型时，发现 C1166/AT1 基因等位基因变异与中风存在显着关联 [未调整的比值比 (OR) = 1.5，95% 置信区间 (Cl) 1.1-2.2，P= 0.024]。这种关联的强度在高血压患者亚组（135 例病例和 110 例对照）中变得更加明显。事实上，在该队列中，AT1 基因的独立 OR 在显性模型中为 2.1，95% Cl 1.2-3.7，P= 0.006，在加法模型中为 2.0,95% Cl 1.3-3.2，P=0.002。没有发现其他 RAAS 基因与中风有关。 结论 我们的研究结果支持 AT1 基因变异在缺血性中风发展中的诱发作用。特别是，AT1基因变异对高血压时缺血性中风的发生产生重大影响。 (C) 2004 年利平科特·威廉姆斯·威尔金斯。
Objective The role of the renin-angiotensin-aldosterone system (RAAS) genes on predisposition to develop stroke, a multifactorial and polygenic cardiovascular trait, is still under investigation. In the present study we characterized the contributory role of RAAS genes in the susceptibility to develop ischemic stroke in humans.Methods Allele and genotype frequencies of RAAS genes were characterized in a population of 215 cases (including only atherothrombotic and lacunar forms) and 236 controls selected in Sardinia, a large Mediterranean island with a well-known segregated population. Statistical analysis was performed in the whole population and, based on a significant interaction between angiotensin II receptor (AT1) genotype and hypertension, was also repeated in the hypertensive subgroup.Results A significant association of the C1166/AT1 gene allelic variant with stroke was found when assuming a dominant model of transmission [unadjusted odds ratio (OR) = 1.5, 95% confidence interval (Cl) 1.1-2.2, P= 0.024]. The strength of the association became more evident in the subgroup of hypertensive individuals (135 cases and 110 controls). In fact, in this cohort the independent OR for the AT1 gene was 2.1, 95% Cl 1.2-3.7, P= 0.006 in the dominant model and 2.0,95% Cl 1.3-3.2, P=0.002 in the additive model. No other RAAS gene was identified as a contributor to stroke.Conclusions Our findings support a predisposing role of an AT1 gene variant in the development of ischemic stroke. In particular, the AT1 gene variant exerted a major impact on ischemic stroke occurrence in the presence of hypertension. (C) 2004 Lippincott Williams Wilkins.