期刊
MOLECULAR NEUROBIOLOGY
卷 54, 期 5, 页码 3195-3204出版社
HUMANA PRESS INC
DOI: 10.1007/s12035-016-9889-z
关键词
HLA; Genetics; Alzheimer's disease; Brain structure; Neuroimaging
资金
- ADNI (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Co
- F. Hoffmann-LaRoche Ltd
- Genetech, Inc.
- GE Healthcare
- Innogenetics, NV
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development LLC
- Medpace, Inc
- Merck Co, Inc.
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Novartis Pharmaceuticals, Co
- Pfizer, Inc.
- Piramal Imaging
- Synarc Inc
- Takeda Pharmaceutical Co.
- Canadian Institutes of Health Research
- National Natural Science Foundation of China [81471309, 81171209, 81371406, 81501103, 81571245]
- Shandong Provincial Outstanding Medical Academic Professional Program
- Qingdao Key Health Discipline Development Fund
- Qingdao Outstanding Health Professional Development Fund
- Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders
- Servier
There is accumulating evidence that the human leukocyte antigen (HLA) gene variants are associated with Alzheimer's disease (AD). However, how they affect AD occurrence is still unknown. In this study, we firstly investigated the association of gene variants in HLA gene variants and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA on AD pathogenesis. We selected hippocampus, hippocampus CA1 subregion, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). According to the previous association studies of HLA variants and AD, 12 SNPs in HLA were identified in the dataset following quality control measures. In total group analysis, our results showed that TNF-alpha SNPs at rs2534672 and rs2395488 were significantly positively associated with the volume of the left middle temporal lobe (rs2534672: P = 0.00035, Pc = 0.004; rs2395488: P = 0.0038, Pc = 0.023) at baseline. In the longitudinal study, HFE rs1800562 was remarkably correlated with the lower atrophy rate of right middle temporal lobe (P = 0.0003, Pc = 0.003) and RAGE rs2070600 was associated with the atrophy rate of right hippocampus substructure-CA1 over 2 years (P = 0.003, Pc = 0.035). Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subgroup analysis, as well as the association of rs2534672 with the baseline volume of the left middle temporal lobe in normal cognition (NC) subgroup analysis. Our study provided preliminary evidences that HLA gene variants might participate in the structural alteration of AD associated brain regions, hence modulating the susceptibility of AD.
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