ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala
ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala
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DOI：
10.1016/j.neurobiolaging.2004.09.011
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发表时间：
2005-08-01
影响因子：
4.2
通讯作者：
van Duijn, CM
中科院分区：
文献类型：
--
作者：
Sleegers, K;den Heijer, T;van Duijn, CM
尽管生物学支持血管紧张素转换酶（ACE）在阿尔茨海默病（AD）中的作用，但评估AD中ACE I/D多态性的研究相互矛盾。我们在鹿特丹研究中重新评估了这种关联，这是一项基于人群的队列研究。通过调整血管因素，并通过分析非痴呆个体的萎缩、白色病变和MRI上的梗死，进一步探讨了相关机制。基因型可用于6488名参与者。在平均6年的随访期间，250名受试者发展为AD。MRI数据可用于494名非痴呆参与者。与携带D等位基因相比，I等位基因的纯合性使AD的风险略有增加（RR 1.12（95% CI 0.99-1.25））。这种增加仅在女性中显著，并且与血管因素无关（RR 1.39（95% CI 1.14-1.69））。非痴呆妇女与11基因型有较小的海马和杏仁核体积。血管病变与ACE无显著相关性。这表明ACE I等位基因纯合子的女性AD和早期AD病理学风险适度但显著增加，与血管因素无关。(c)2004年爱思唯尔公司All rights reserved.
Despite biological support for a role of angiotensin converting enzyme (ACE) in Alzheimer's disease (AD), studies assessing the ACE I/D polymorphism in AD are conflicting. We re-evaluated this association in the Rotterdam Study, a population-based cohort study. The mechanism of association was further explored by adjusting for vascular factors, and by analysing atrophy, white matter lesions and infarcts on MRI in non-demented individuals. Genotypes were available for 6488 participants. During average follow-up of 6 years 250 subjects developed AD. MRI data were available for 494 non-demented participants. Homozygosity for the I-allele conferred a slightly increased risk of AD compared to carrying a D-allele (RR 1.12 (95% CI 0.99-1.25)). This increase was only significant in women, and independent of vascular factors (RR 1.39 (95% CI 1.14-1.69)). Non-demented women with the 11 genotype had smaller hippocampal and amygdalar volumes. Vascular pathology was not significantly associated with ACE. This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors. (c) 2004 Elsevier Inc. All rights reserved.