Tian J, Shi J, Bailey K, Harris J M, Pritchard A, Lambert J-C, Chartier-Harlin M-C, Pickering-Brown S M, Lendon C L, Mann D M A
Clinical Neuroscience Research Group, Department of Medicine, University of Manchester, Manchester, M13 9PT, UK.
Neurosci Lett. 2004 Jan 9;354(2):103-6. doi: 10.1016/j.neulet.2003.09.072.
The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele.
在93例经尸检确诊的阿尔茨海默病（AD）患者中，研究血管紧张素1转换酶（ACE）基因插入（I）/缺失（D）（I/D）多态性对大脑皮质四个区域白质髓鞘丢失（ML）程度的影响。评估了APO E ε4等位基因与ACE D等位基因协同作用的可能影响。当合并来自所有四个脑区的数据时，D/D、I/D和I/I基因型组之间的ML程度没有差异。然而，单独分析显示，与I/D和I/I基因型患者相比，D/D基因型患者的额叶和颞叶皮质受ML影响更严重。根据APO E ε4等位基因分层显示，携带至少一个ACE D等位基因拷贝和一个APO E ε4等位基因的患者总体ML更大，尤其是两者均为纯合子的个体。因此，APO E ε4等位基因可能在携带ACE D/D基因型的AD患者（和其他受试者）中协同作用，增加ML风险，可能是通过与APO E ε4等位基因患者冠状动脉粥样硬化相关的心输出量降低导致的短暂缺血发作。
