Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasma lipidic pattern
Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasma lipidic pattern
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DOI：
10.1159/000051237
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发表时间：
2001-03-01
影响因子：
2.4
通讯作者：
Corbo, RM
中科院分区：
文献类型：
--
作者：
Scacchi, R;Gambina, G;Corbo, RM
载脂蛋白E基因调控区域的两个新的多态性-491 A/T和-427 T/C被报道与阿尔茨海默病（AD）的风险相关。此外，体外研究表明，这两种多态性调节apoE蛋白的表达水平。我们在一系列老年迟发散发性AD患者和年龄匹配的对照组中检测了这两种多态性，以及LDL受体基因的Mspl多态性，但未能发现这些遗传特征与AD风险增加之间的任何关联。在相同的样本中，我们研究了不同基因型与血浆脂质水平之间的关系。由于众所周知的三等位基因APOE多态性对血脂水平的影响可能掩盖了其他多态性的影响，因此在进行分析时考虑了APOE基因型。两个调控区多态性仅对apoE水平有显著影响。-427 TT纯合子的apoE水平较低，-491 AA纯合子的apoE水平高于其他基因型。这一结果在体内证实了已经观察到的-491 P/T和-427 T/C多态性对APOE启动子转录活性的体外影响。版权所有(C) 2001 S. Karger AG，巴塞尔
Two new polymorphisms in the regulatory region of the apolipoprotein E gene, -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the Mspl polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 P/T and -427 T/C polymorphisms on APOE promoter transcription activity. Copyright (C) 2001 S. Karger AG, Basel.