Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension
Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension
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DOI：
10.1161/01.hyp.33.3.844
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发表时间：
1999-03-01
期刊：
影响因子：
8.3
通讯作者：
Kontula, K
中科院分区：
文献类型：
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作者：
Kainulainen, K;Perola, M;Kontula, K
肾素-血管紧张素系统的组成部分在血压的正常调节中起着重要作用。我们对芬兰高血压双胞胎和他们受影响的兄弟姐妹中涉及肾素-血管紧张素级联反应的基因进行了全面的遗传连锁研究。在142个家系的329名高血压患者中，我们没有发现高血压与肾素、血管紧张素原、血管紧张素转换酶或激肽释放酶1编码基因之间存在关联的证据。相比之下，I型血管紧张素II受体(AT(1))的两个基因内标记在总样本中显示出一些连锁的证据。对这一基因座进行了更仔细的研究，使用的是非肥胖同胞对的亚组，这些人起病早，地理来源一致。这些分层提供了高血压与包含AT(1)基因的遗传区相关联的暗示证据，其最大多点几率对数(LOD)得分为3.9。对50例高血压患者和122例正常血压对照进行的遗传关联研究表明，AT基因A1166-->；C等位基因频率在高血压个体中增加。在一种允许连锁不平衡的无模型多点连锁分析的新变种中，获得了5.13的LOD分数。对8个索引样本的DNA样本中的整个编码区和848bp的序列分析没有发现以前未发表的序列变异。这些数据提供了证据，证明在芬兰人群中，AT(1)基因座的一个常见的遗传变异会影响原发性高血压的风险。
Components of the renin-angiotensin system play an important role in the normal regulation of blood pressure. We carried out a comprehensive genetic linkage study of the genes involved in the renin-angiotensin cascade in Finnish hypertensive twins and their affected siblings. We found no evidence for linkage between essential hypertension and the genes coding for renin, angiotensinogen, angiotensin-converting enzyme, or kallikrein 1 in the 329 hypertensive individuals of 142 families studied. In contrast, two intragenic markers for the type I angiotensin II receptor (AT(1)) showed some evidence for linkage in the total sample. A closer examination of this gene locus was carried out using subgroups of nonobese sibpairs with early onset of hypertension and uniform geographical origin. These stratifications yielded suggestive evidence for linkage of hypertension to the genetic area containing the AT(1) gene, with a maximal multipoint logarithm of the odds (LOD) score of 3.9. A genetic association study carried out in an independent series of 50 hypertensive cases and 122 normotensive controls showed an increase in the frequency of the A1166-->C allele of the AT, gene in the hypertensive individuals. In a novel variant of model-free multipoint linkage analysis allowing linkage disequilibrium in the calculations, an LOD score of 5.13 was obtained. Sequence analyses of the entire coding region and 848 bp of promoter region in the DNA sample on 8 index samples did not reveal previously unpublished sequence variations. The data provide evidence that a common genetic variant of the AT(1) gene locus influences the risk of essential hypertension in the Finnish population.