关注健康老龄化，APOE ε4等位基因增强有毒金属及其混合物与老年人认知功能障碍的有害影响

APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults

APOE ε4等位基因修饰有毒金属及其混合物与老年人认知功能障碍的关联

Authors: Qiang Liu ^{a 1}, Junzhe Li ^{a 1}, Xuqiu Cheng ^{a 1}, Guimei Chen ^{b 1}, Yan Zhang ^a, Ziwei Tian ^a, Yuan Wang ^a, Hongli Wang ^a, Xianwei Guo ^a, Huaibiao Li ^c, Liang Sun ^c, Bing Hu ^c, Dongmei Zhang ^b, Chunmei Liang ^d, Jie Sheng ^e, Fangbiao Tao ^f, Jun Wang ^g, Linsheng Yang ^a *

Source: Environmental Research. Volume 255, 15 August 2024, 119148.

Doi: 10.1016/j.envres.2024.119148.

Abstract

Background: The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people.

Methods: A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment.

Results: Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (P_trend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively.

Conclusions: APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

Keywords: Toxic metal mixture; Apolipoprotein E ε4 gene; Cognitive impairment; Older adults; Modification

背景 有毒金属（TM）混合物与载脂蛋白E（APOE）ε4基因交互作用对老年人认知功能障碍影响的证据很少。本研究旨在探讨单一TMs及其混合物与中国社区老年人认知障碍的关联是否依赖于APOE ε4。

方法 该研究的数据来源于一项队列研究的基线调查的一个子集，共纳入1148名老年人作为研究对象。采用电感耦合等离子体质谱法测定血砷（As）、镉（Cd）、铅（Pb）、锶（Sr）和钒（V）。采用聚合酶链反应（PCR）仪检测APOE基因（rs429358、rs7412）多态性。采用混合效应logistic回归分析单个TMs及APOE基因型与认知障碍的关联。采用加权分位数和（WQS）模型和贝叶斯核机器回归（BKMR）模型分析TM混合物对认知障碍的联合影响，以及TM混合物与APOE ε4基因型的交互作用对认知障碍的影响。

结果 校正协变量后，Pb与认知功能障碍几率增加呈显著的线性相关（P_trend = 0.045）。而APOE基因型与认知功能障碍无显著相关性。WQS结果显示，TM混合物使认知障碍的发生风险增加31.0% (OR=1.31, 95% CI: 0.92, 1.87)，但无统计学意义。BKMR显示TM混合物与认知障碍之间存在显著的线性关联。此外，WQS和BKMR结果均表明，Pb在混合物中对认知障碍的贡献最大。Pb/TM混合物与APOE基因型对认知障碍均有显著交互作用，分别占总效应的38.1%和38.2%。

结论 APOE ε4等位基因增强了单一Pb或TM混合物与认知障碍的关联。这些发现可能有助于发展精确预防。

关键词 有毒金属混合物；载脂蛋白E ε4基因；认知功能障碍；老年人；效应修饰