Ma Jing, Zhang Wei, Tan Lin, Wang Hui-Fu, Wan Yu, Sun Fu-Rong, Tan Chen-Chen, Yu Jin-Tai, Tan Lan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
Oncotarget. 2016 Sep 13;7(37):58779-58788. doi: 10.18632/oncotarget.9563.
Membrane-spanning 4-domains, subfamily A, member 6A (MS4A6A) has been identified as susceptibility loci of Alzheimer's disease (AD) by several recent genome-wide association studies (GWAS), whereas little is known about the potential roles of these variants in the brain structure and function of AD. In this study, we included a total of 812 individuals from the Alzheimer's disease Neuroimaging Initiative (ADNI) database. Using multiple linear regression models, we found MS4A6A genotypes were strongly related to atrophy rate of left middle temporal (rs610932: Pc = 0.017, rs7232: Pc = 0.022), precuneus (rs610932: Pc = 0.015) and entorhinal (rs610932, Pc = 0.022) on MRI in the entire group. In the subgroup analysis, MS4A6A SNPs were significantly accelerated the percentage of volume loss of middle temporal, precuneus and entorhinal, especially in the MCI subgroup. These findings reveal that MS4A6A genotypes affect AD specific brain structures which supported the possible role of MS4A6A polymorphisms in influencing AD-related neuroimaging phenotypes.
跨膜4结构域A亚家族成员6A(MS4A6A)已被多项近期全基因组关联研究(GWAS)确定为阿尔茨海默病(AD)的易感基因座,而这些变体在AD脑结构和功能中的潜在作用却知之甚少。在本研究中,我们纳入了来自阿尔茨海默病神经影像倡议(ADNI)数据库的总共812名个体。使用多元线性回归模型,我们发现MS4A6A基因型与全组MRI上左中颞叶(rs610932:Pc = 0.017,rs7232:Pc = 0.022)、楔前叶(rs610932:Pc = 0.015)和内嗅区(rs610932,Pc = 0.022)的萎缩率密切相关。在亚组分析中,MS4A6A单核苷酸多态性显著加速了中颞叶、楔前叶和内嗅区的体积丢失百分比,尤其是在轻度认知障碍(MCI)亚组中。这些发现表明,MS4A6A基因型影响AD特异性脑结构,这支持了MS4A6A多态性在影响AD相关神经影像表型中的可能作用。