Angiotensin II type 1 receptor 1166C polymorphism is associated with abdominal aortic aneurysm in three independent cohorts
Angiotensin II type 1 receptor 1166C polymorphism is associated with abdominal aortic aneurysm in three independent cohorts
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DOI：
10.1161/atvbaha.107.155564
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发表时间：
2008-04-01
影响因子：
8.7
通讯作者：
van Rij, Andre M.
中科院分区：
文献类型：
--
作者：
Jones, Gregory T.;Thompson, Andrew R.;van Rij, Andre M.
目的-尽管RAS系统基因的多态性变异以前与AAA的易感性相关，但此类研究受到样本量小的显著限制。本研究采用迄今报道的最大病例系列，以确定RAS的常见遗传变异是否与AAA的易感性或严重性相关。方法和结果-在3个地理上不同但种族相似的病例对照队列中研究了与肾素-血管紧张素系统相关的4种常见基因变异的频率，结果将1226例AAA病例与1723例对照进行比较。在所有3个中，AGTR 1 1166 C等位基因在AAA患者中比对照组明显更常见（总体校正OR 1.60，95% CI 1.32至1.93，P = 1.1 x 10（-6））。总体而言，ACE ID基因型与AAA相关（OR 1.33，95% CI 1.06至1.67，P < 0.02）。AGT 268 T等位基因出现了上位效应对大动脉瘤size. Conclusion，这项研究已经确定了一个强大的和重复的AGTR 1 1166 C等位基因和AAA的易感性之间的关联，和较弱的效果与ACE缺失等位基因，在3个地理上不同，但种族相似，病例对照队列。本研究强调了RAS在AAA中的关键作用，并强调需要在合适的独立队列中复制和验证结果。
Objectives-Although polymorphic variations in genes of the RAS system have previously been associated with susceptibility to AAA, such studies have been significantly limited by small sample sizes. This study was undertaken, using the largest case series yet reported, to determine whether common genetic variants of the RAS are associated with either susceptibility or severity of AAA.Methods and Results-The frequencies of 4 common genetic variants of genes related to the renin-angiotensin system were investigated in 3 geographically distinct, but ethnically similar, case-control cohorts, resulting in comparison of 1226 AAA cases with 1723 controls. In all 3 the AGTR1 1166C allele was significantly more common in AAA patients than controls (overall adjusted OR 1.60, 95% CI 1.32 to 1.93, P = 1.1 x 10(-6)). Overall, the ACE ID genotype was associated with AAA (OR 1.33, 95% CI 1.06 to 1.67, P < 0.02). The AGT 268T allele appeared to have an epistatic effect on large aneurysm size.Conclusion-This study has identified a strong and repeated association between the AGTR1 1166C allele and susceptibility to AAA, and a weaker effect associated with the ACE deletion allele, in 3 geographically distinct, but ethnically similar, case-control cohorts. This study highlights the key role of the RAS in AAA and emphasizes the need for replication and validation of results in suitable independent cohorts.