Effect of Interaction of ATG7 and Plasma Metal Concentrations on Cognitive Impairment in Rural China

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2025-02-24 DOI:10.1007/s12031-025-02322-x

Xu Tang, Jiejing Cao, Jiansheng Cai, Xiaoting Mo, Yanfei Wei, Kailian He, Zeyan Ye, Yu Jian Liang, Linhai Zhao, Lidong Qin, You Li, Jian Qin, Zhiyong Zhang

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引用次数: 0

Abstract

The objective of this study is to explore the association of plasma metal concentrations with impaired cognitive function in different genotypes of ATG7 using multiple models. A cross-sectional survey was conducted in rural China among 994 individuals aged 30 years or older. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Genetic analysis focused on two single-nucleotide polymorphisms (SNPs) in the autophagy-related gene ATG7 (rs2606757 and rs8154). Plasma concentrations of metals were quantified using inductively coupled plasma mass spectrometry. Restricted cubic splines were used to explore the association between serum metal concentration and the occurrence of mild cognitive impairment in individuals with various genotypes. Bayesian Kernel Machine Regression (BKMR) models were used to explore the interactions between individual metals. In a restricted cubic spline model, there is a nonlinear relationship between plasma concentration of Cd and the occurrence of cognitive impairment in individuals carrying the AA (P of Nonlinear = 0.008) and AT (P of Nonlinear = 0.007) genotypes at the rs2606757. However, in people carrying the TT genotype at the rs2606757 locus, the concentration of metals in plasma was not significantly associated with cognitive impairment (P of Nonlinear = 0.534). The results of the BKMR model are consistent with those of the restricted cubic spline model. The TT genotype at rs2606757 in ATG7 appears to confer greater cognitive resilience against Cd-induced cognitive damage. These findings highlight the importance of considering gene-environment interactions in the context of cognitive impairment and suggest potential avenues for preventing cognitive decline in individuals exposed to Cd. Further research is needed to elucidate the precise mechanisms underlying these interactions.

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ATG7与血浆金属浓度相互作用对中国农村认知功能障碍的影响

本研究的目的是通过多种模型探讨不同基因型ATG7患者血浆金属浓度与认知功能受损的关系。在中国农村对994名年龄在30岁以上的人进行了横断面调查。采用简易精神状态检查（MMSE）评估认知功能。遗传分析的重点是自噬相关基因ATG7的两个单核苷酸多态性（rs2606757和rs8154）。用电感耦合等离子体质谱法定量测定了血浆中金属的浓度。采用限制性三次样条法探讨不同基因型个体血清金属浓度与轻度认知障碍发生的关系。贝叶斯核机回归（BKMR）模型用于探索单个金属之间的相互作用。在受限三次样条模型中，rs2606757基因型AA（非线性P = 0.008）和AT（非线性P = 0.007）个体的血浆Cd浓度与认知功能障碍的发生存在非线性关系。然而，在rs2606757位点携带TT基因型的人群中，血浆中金属浓度与认知功能障碍无显著相关性（非线性P = 0.534）。BKMR模型的结果与限制三次样条模型的结果一致。ATG7中rs2606757的TT基因型似乎赋予了对cd诱导的认知损伤更大的认知恢复能力。这些发现强调了在认知障碍的背景下考虑基因-环境相互作用的重要性，并提出了预防Cd暴露个体认知能力下降的潜在途径。需要进一步的研究来阐明这些相互作用的确切机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.