Wang Zi-Xuan, Wang Hui-Fu, Tan Lin, Sun Fu-Rong, Tan Meng-Shan, Tan Chen-Chen, Jiang Teng, Tan Lan, Yu Jin-Tai
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Mol Neurobiol. 2017 May;54(4):2469-2476. doi: 10.1007/s12035-016-9832-3. Epub 2016 Mar 15.
HLA-A is a locus of the major histocompatibility complex situated on chromosome 6p21.3. HLA-A has been shown to be associated with susceptibility to Alzheimer's disease (AD). In this study, we firstly investigated the association of gene variants in HLA-A and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA-A on AD pathogenesis. We selected the hippocampus, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). In hybrid population analysis, our results showed a marginally significant association between rs9260168 and the atrophy of the left parahippocampus (P = 0.007, Pc = 0.054), rs3823342 and the atrophy of the left parahippocampus (P = 0.014, Pc = 0.054), rs76475517, which only exists in Caucasians with HLA-A23 or HLA-A24 alleles, and the atrophy of the right amygdala (P = 0.010, Pc = 0.085) at baseline. In particular, the haplotype (TGACAAGG), as a surrogate marker of HLA-A2, was founded to be positively associated with the atrophy of the right hippocampus (P = 0.047) at baseline. Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subpopulation analysis. Our study provided preliminary evidences supporting HLA-A2 in Caucasians contribute to the risk of AD by modulating the alteration of hippocampal volume and HLA-A gene variants appear to play a role in altering AD-related brain structures on MRI.
HLA - A是主要组织相容性复合体的一个基因座，位于6号染色体p21.3区域。研究表明，HLA - A与阿尔茨海默病（AD）易感性相关。在本研究中，我们首先在来自阿尔茨海默病神经影像倡议（ADNI）的大样本中，研究了HLA - A基因变异与MRI上脑结构的关联，以探讨HLA - A对AD发病机制的影响。我们选择海马体、海马旁回、后扣带回、楔前叶、颞中回、内嗅皮质和杏仁核作为感兴趣区域（ROI）。在混合人群分析中，我们的结果显示，rs9260168与左侧海马旁回萎缩之间存在边缘显著关联（P = 0.007，Pc = 0.054），rs3823342与左侧海马旁回萎缩之间存在边缘显著关联（P = 0.014，Pc = 0.054），rs76475517（仅存在于携带HLA - A23或HLA - A24等位基因的白种人中）与基线时右侧杏仁核萎缩之间存在边缘显著关联（P = 0.010，Pc = 0.085）。特别是，单倍型（TGACAAGG）作为HLA - A2的替代标志物，被发现与基线时右侧海马体萎缩呈正相关（P = 0.047）。此外，我们在轻度认知障碍（MCI）亚组分析中检测到了上述四种关联。我们的研究提供了初步证据，支持白种人中的HLA - A2通过调节海马体体积变化导致AD风险增加，并且HLA - A基因变异似乎在改变MRI上与AD相关的脑结构中发挥作用。
