Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families.
Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families.
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DOI：
10.1016/j.neurobiolaging.2009.02.014
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发表时间：
2011-02
影响因子：
4.2
通讯作者：
MIRAGE Study Group
中科院分区：
文献类型：
--
作者：
Cuenco KT;Friedland R;Baldwin CT;Guo J;Vardarajan B;Lunetta KL;Cupples LA;Green RC;DeCarli C;Farrer LA;MIRAGE Study Group
体外和动物模型研究表明，甲状腺素运载蛋白（TTR）抑制淀粉样β蛋白的产生，淀粉样β蛋白是阿尔茨海默病（AD）发病机制的主要贡献者。我们评估了16个TTR单核苷酸多态性（SNPs）与AD风险的关联，来自MINUS研究的158个非洲裔美国人和469个高加索人不一致的同胞。没有证据表明TTR与AD在两个人群样本中存在关联。为了研究TTR SNPs影响AD过程特定组分的可能性，我们在48个非洲裔美国人和265个高加索同胞的子集中测试了这些SNPs与通过磁共振成像（MRI）定义的神经变性和脑血管疾病的四项指标的关联。在高加索人样本中，7种常见SNPs中的5种和几种单倍型与海马萎缩显著相关。这些SNPs中的两个也显示出在非裔美国人样本中存在关联的边缘证据。其他MRI特征的结果不显著。这项研究强调了神经影像学内表型作为发现影响AD发病机制的基因的工具的潜在价值。
In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.
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