Reassessment of Risk Genotypes (GRN, TMEM106B, and ABCC9 Variants) Associated With Hippocampal Sclerosis of Aging Pathology
Reassessment of Risk Genotypes (GRN, TMEM106B, and ABCC9 Variants) Associated With Hippocampal Sclerosis of Aging Pathology
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DOI：
10.1097/nen.0000000000000151
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Fardo, David W.
中科院分区：
文献类型：
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作者：
Nelson, Peter T.;Wang, Wang-Xia;Fardo, David W.
海马衰老硬化症（HS-Aging）是老年人常见的高发病率神经退行性疾病。为了了解 HS-Aging 的危险因素，我们分析了阿尔茨海默病遗传学联盟的数据，并将这些数据与国家阿尔茨海默病协调中心数据库的临床和病理信息相关联。总体而言，纳入了 268 名患有 HS-Aging 的研究志愿者和 2,957 名对照者；所有人都可以获得详细的神经病理学数据。该研究重点关注先前与 HS 老化风险相关的单核苷酸多态性：rs5848 (GRN)、rs1990622 (TMEM106B) 和 rs704180 (ABCC9)。对先前未评估的子样本（51 个 HS-Aging 病例和 561 个对照）的分析复制了先前确定的 HS-Aging 风险等位基因的关联。为了测试基因-基因相互作用和基因型-表型关系的证据，对汇总数据进行了分析。与这些基因多态性相关的 HS-Aging 诊断风险并不继发于阿尔茨海默病或痴呆与路易体神经病理学变化的关联。多种风险基因型的存在与 HS-Aging 病理的附加风险趋势相关。我们得出结论，多个基因在 HS-Aging 中发挥重要作用，这是一种独特的衰老神经退行性疾病。
Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer's Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer's Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 (GRN), rs1990622 (TMEM106B), and rs704180 (ABCC9). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases and 561 controls) replicated the associations of previously identified HS-Aging risk alleles. To test for evidence of gene-gene interactions and genotype-phenotype relationships, pooled data were analyzed. The risk for HS-Aging diagnosis associated with these genetic polymorphisms was not secondary to an association with either Alzheimer disease or dementia with Lewy body neuropathologic changes. The presence of multiple risk genotypes was associated with a trend for additive risk for HS-Aging pathology. We conclude that multiple genes play important roles in HS-Aging, which is a distinctive neurodegenerative disease of aging.