Jones Gregory T, Thompson Andrew R, van Bockxmeer Frank M, Hafez Hany, Cooper Jackie A, Golledge Jonathan, Humphries Stephen E, Norman Paul E, van Rij Andre M
Department of Surgery, University of Otago, New Zealand.
Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):764-70. doi: 10.1161/ATVBAHA.107.155564. Epub 2008 Jan 31.
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.
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=1.1x10(-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.
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.
尽管RAS系统基因的多态性变异先前已被认为与腹主动脉瘤易感性相关，但此类研究因样本量小而受到显著限制。本研究采用迄今报道的最大病例系列，以确定RAS常见基因变异是否与腹主动脉瘤的易感性或严重程度相关。
在3个地理位置不同但种族相似的病例对照队列中，研究了肾素-血管紧张素系统相关基因的4种常见基因变异的频率，共比较了1226例腹主动脉瘤病例和1723例对照。在所有3个队列中，AGTR1 1166C等位基因在腹主动脉瘤患者中比对照显著更常见（总体调整后的OR为1.60，95%CI为1.32至1.93，P = 1.1×10⁻⁶）。总体而言，ACE ID基因型与腹主动脉瘤相关（OR为1.33，95%CI为1.06至1.67，P < 0.02）。AGT 268T等位基因似乎对大动脉瘤大小有上位效应。
本研究在3个地理位置不同但种族相似的病例对照队列中，发现AGTR1 1166C等位基因与腹主动脉瘤易感性之间存在强烈且重复的关联，以及与ACE缺失等位基因相关的较弱效应。本研究突出了RAS在腹主动脉瘤中的关键作用，并强调需要在合适的独立队列中重复和验证结果。
