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铝暴露与载脂蛋白Eε4基因对在职员工认知功能的相互作用。

Interaction between aluminum exposure and ApoEε4 gene on cognitive function of in-service workers.

作者信息

Wang Shanshan, Xue Yingjun, Zhang Jintao, Meng Huaxing, Zhang Jingsi, Li Xiaoyan, Zhang Zhuoran, Li Huan, Pan Baolong, Lu Xiaoting, Zhang Qinli, Niu Qiao

机构信息

Section of Occupational Medicine, Department of Special Medicine, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.

出版信息

Chemosphere. 2023 May;323:138282. doi: 10.1016/j.chemosphere.2023.138282. Epub 2023 Mar 1.

DOI:10.1016/j.chemosphere.2023.138282
PMID:36868418
Abstract

The occurrence and development of cognitive impairment, the early stage of AD, may be affected both by factors of environmental (aluminum exposure) and genetic (ApoEε4 gene). But whether there is an interaction between the two factors on cognitive function is still unknown. To explore the interaction between the two factors on cognitive function of in-service workers. A total of 1121 in-service workers in a large aluminum factory were investigated in Shanxi Province. Cognitive function was assessed by the Mini-mental State Examination (MMSE), the clock-drawing test (CDT), the Digit Span Test (DST, including DSFT and DSBT), the fuld object memory evaluation (FOM), and the verbal fluency task (VFT). The plasma-Al (p-Al) concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator, and the participants were divided into four Al exposure groups according to the quartile of p-Al concentrations, namely Q1, Q2, Q3, and Q4. ApoE genotype was determined by Ligase Detection Reaction (LDR). The multiplicative model was fitted using non-conditional logistic regression and additive model was fitted using crossover analysis to analyze the interaction between p-Al concentrations and the ApoEε4 gene. Finally, a dose-response relationship between p-Al concentrations and cognitive impairment was observed, with the p-Al concentrations increased, cognitive function performance gradually becomes worse (P<0.05), and the risk of cognitive impairment gradually increases (P<0.05), mainly in executive/visuospatial impairment, auditory memory impairment (particularly the working memory impairment). And ApoEε4 gene may be a risk factor for cognitive impairment, while no association between the ApoEε2 gene and cognitive impairment is observed. Additionally, an additive but no multiplicative interaction between p-Al concentrations and ApoEε4 gene is observed, and when the two factors work together, the risk of cognitive impairment further increased, of which 44.2% can be attributed to the interaction effect.

摘要

认知障碍(阿尔茨海默病的早期阶段)的发生和发展可能受到环境因素(铝暴露)和遗传因素(载脂蛋白Eε4基因)的影响。但这两种因素在认知功能上是否存在相互作用仍不清楚。为了探究这两种因素在在职员工认知功能上的相互作用。对山西省一家大型铝厂的1121名在职员工进行了调查。通过简易精神状态检查表(MMSE)、画钟试验(CDT)、数字广度测试(DST,包括数字广度顺背试验和数字广度倒背试验)、富尔德物体记忆评估(FOM)和语言流畅性任务(VFT)对认知功能进行评估。通过电感耦合等离子体质谱法(ICP-MS)测量血浆铝(p-Al)浓度作为内部暴露指标,并根据p-Al浓度的四分位数将参与者分为四个铝暴露组,即Q1、Q2、Q3和Q4。通过连接酶检测反应(LDR)确定载脂蛋白E基因型。使用非条件逻辑回归拟合乘法模型,使用交叉分析拟合加法模型来分析p-Al浓度与载脂蛋白Eε4基因之间的相互作用。最后,观察到p-Al浓度与认知障碍之间存在剂量反应关系,随着p-Al浓度升高,认知功能表现逐渐变差(P<0.05),认知障碍风险逐渐增加(P<0.05),主要表现为执行/视觉空间障碍、听觉记忆障碍(尤其是工作记忆障碍)。并且载脂蛋白Eε4基因可能是认知障碍的一个危险因素,而未观察到载脂蛋白Eε2基因与认知障碍之间存在关联。此外,观察到p-Al浓度与载脂蛋白Eε4基因之间存在相加但无相乘的相互作用,当这两种因素共同作用时,认知障碍风险进一步增加,其中44.2%可归因于相互作用效应。

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