中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (6): 653-660.doi: 10.4103/1673-5374.130117

• 原著:退行性病与再生 • 上一篇    下一篇

APOE和APOC1基因变异参与中国晚发型阿尔茨海默病患者认知功能下降

  

  • 收稿日期:2014-02-13 出版日期:2014-03-22 发布日期:2014-03-22
  • 基金资助:

    广西科学研究与技术开发计划(1355005-6-2)。国家自然科学基金(30972709, 81061120527, 81241082, 81000780, 81370445),卫生部部署(管)医院临床学科重点项目(10120101),卫生部公益性行业科研基金(201302008),中国国家科技支撑计划课题(2012BAI10B01),加拿大健康研究基金(#109606)

APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer’s disease

Qin Zhou 1, 2, Dantao Peng 1, Xinrui Yuan 1, Zeping Lv 2, Shenghang Pang 2, Wenyu Jiang 2, Chuyu Yang 2, Xiaohong Shi 1, Guofang Pang 2, Yige Yang 1, Haiqun Xie 2, Wandong Zhang 3, Caiyou Hu 2, Ze Yang 1   

  1. 1 Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China
    2 Department of Neurology, Jiangbin Hospital, Nanning, Guangxi Zhuang Autonomous Region, China
    3 Human Health Therapeutics, National Research Council of Canada, Ottawa, Canada
  • Received:2014-02-13 Online:2014-03-22 Published:2014-03-22
  • Contact: Caiyou Hu, Department of Neurology, Jiangbin Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China. cyhu.hua@163.com; Wandong Zhang, Human Health Therapeutics, National Research Council of Canada, Ottawa, Canada. wandong.zhang@nrc-cnrc.gc.ca; Ze Yang, Key Laboratory of Geriatrics, Beijing Hospital& Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. yixueshengzhouqin@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81370445, 81061120527, 81241082; Major Funding from Beijing Hospital, No. BJ-2010-30; Key Project of Clinical Disciplines at the Subordinate Hospital, Ministry of Health, No. 10120101; National Department Public Benefit Research Foundation by the Ministry of Health, No. 201302008; 12th 5-year National Program from Ministry of Scientific Technology, No. 2012BAI10B01; Science and Technology Development Foundation of Guangxi Zhuang Autonomous Region, No. 1355005-6-2; and Canadian Institute of Health Research (CIHR), No. 109606.

摘要:

目前APOE,APOC1和LRP基因多态性与晚发型阿尔茨海默病患者的认知功能下降是否有关联目前尚不清晰。为此,我们纳入了78例中国广西壮族自治区汉族晚发型阿尔茨海默病患者,采用限制性片段长度多态性聚合酶链式反应对APOE,APOC1和LRP基因进行分型。采用简易智能量表和临床痴呆量表评价患者的认知功能。随访30个月后发现,携带APOE ε4基因的患者简易智能量表的总分下降趋势、出现认知功能进展情况、携带APOC1 H2等位基因患者比例明显高于不携带APOE ε4的患者。认知功能进展的患者较未达到认知功能进展的患者APOE ε4等位基因频率更高。结果证实APOE ε4基因可能在中国晚发型阿尔茨海默病患者认知功能的下降过程中发挥重要作用,且可能与APOC1 H2存在协同作用共同增加了认知功能下降的风险。

关键词: 神经再生, 神经退行性变, 记忆动能紊乱, 认知功能障碍, 痴呆, 阿尔茨海默病, 基因, 多态性, 载脂蛋白E, 载脂蛋白C-I, 低密度脂蛋白相关受体蛋白

Abstract:

Current evidence shows that apolipoprotein E (APOE), apolipoprotein CI (APOC1) and low density lipoprotein receptor-related protein (LRP) variations are related to late-onset Alzheimer’s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer’s disease patients. We performed a 30-month longitudinal cohort study to investigate the relationship between Alzheimer’s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer’s disease were recruited form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess patients’ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE ε4 carriers compared with non-carriers. In addition, the APOE ε4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive impairment progression group. In conclusion, APOE ε4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ε4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer’s disease.

Key words: nerve degeneration, cognitive disorders, dementia, Alzheimer’s disease, polymorphism, apolipoprotein E, apolipoprotein CI, low density lipoprotein receptor-related protein, NSFC grant, neural regeneration