环境危险因素影响的机制研究一直在探索 microRNA (miRNA) 作为临床疾病可能途径的潜在作用。在这项研究中，我们检查脚趾甲金属水平是否与细胞外 miRNA (ex-miRNA) 表达的变化相关。我们使用 1996 年至 2014 年规范老化研究中的数据进行分析。我们使用典型相关分析 (CCA) 和纵向中值回归研究了测量的趾甲金属（砷、镉、铅、锰和汞）与该人群中 282 个 ex-miRNA 之间的关联。我们调整了年龄、教育程度、体重指数、饮酒和吸烟行为、糖尿病以及海鲜消费（如果有）等协变量。从回归分析获得的 p 值经过多重比较校正。使用通路分析进一步检查了与脚趾甲金属水平相关的 Ex-miRNA。我们的数据集包括来自 589 名基线平均年龄为 72.9 岁的男性的 937 个观察结果。我们的相关性和回归分析都确定铅和镉是与 ex-miRNA 表达最密切相关的暴露量。许多 ex-miRNA 被鉴定为与趾甲金属水平相关。尤其是 miR-27b-3p，被发现与 CCA 中的第一规范维度具有高度相关性，并且在回归分析中与镉显着相关。通路分析揭示了 ex-miRNA 的信使 RNA (mRNA) 靶标，这些靶标与许多临床疾病相关，包括癌症、心血管疾病和神经系统疾病等。结论：脚趾甲金属与脚趾甲中 ex-miRNA 水平的变化有关。相关分析和回归分析。鉴定出的 ex-miRNA 可能与多种临床疾病有关。需要进一步研究来验证这些发现。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression.We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses. We looked at associations between measured toenail metals: arsenic, cadmium, lead, manganese, and mercury and 282 ex-miRNAs in this population using canonical correlation analyses (CCAs) and longitudinal median regression. We adjusted for covariates such as age, education, body mass index, drinking and smoking behaviors, diabetes, and where available, seafood consumption. The p-values obtained from regression analyses were corrected for multiple comparisons. Ex-miRNAs identified to be associated with toenail metal levels were further examined using pathway analyses.Our dataset included 937 observations from 589 men with an average age of 72.9 years at baseline. Both our correlation and regression analyses identified lead and cadmium as exposures most strongly associated with ex-miRNA expression. Numerous ex-miRNAs were identified as being associated with toenail metal levels. miR-27b-3p, in particular, was found to have high correlation with the first canonical dimension in the CCA and was significantly associated with cadmium in the regression analysis. Pathway analyses revealed messenger RNA (mRNA) targets for the ex-miRNAs that were associated with a number of clinical disorders including cancer, cardiovascular disease, and neurological disorders, etc. CONCLUSION: Toenail metals were associated with changes in ex-miRNA levels in both correlational and regression analyses. The ex-miRNAs identified can be linked to a variety of clinical disorders. Further studies are required to validate these findings.Copyright © 2024 Elsevier Inc. All rights reserved.