Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Public Health, Shihezi University School of Medicine, Shihezi, 832000, Xinjiang, China.
Environ Pollut. 2022 Jan 1;292(Pt B):118452. doi: 10.1016/j.envpol.2021.118452. Epub 2021 Nov 1.
The present study aims to determine the associations of multiple plasma metal levels and plasma microRNAs (miRNAs) with diabetes risk, and further explore the mediating effects of plasma miRNAs on the associations of plasma metal with diabetes risk. We detected plasma levels of 23 metals by inductively coupled plasma mass spectrometry (ICP-MS) among 94 newly diagnosed and untreated diabetic cases and 94 healthy controls. The plasma miRNAs were examined by microRNA Array screening and Taqman real-time PCR validation among the same study population. The multivariate logistic regression models were employed to explore the associations of plasma metal and miRNAs levels with diabetes risk. Generalized linear regression models were utilized to investigate the relationships between plasma metal and plasma miRNAs, and mediation analysis was used to assess the mediating effects of plasma miRNAs on the relationships between plasma metals and diabetes risk. Plasma aluminum (Al), titanium (Ti), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), barium (Ba), and Thallium (Tl) levels were correlated with elevated diabetic risk while molybdenum (Mo) with decreased diabetic risk (P < 0.05 after FDR multiple correction). MiR-122-5p and miR-3141 were positively associated with diabetes risk (all P < 0.05). Ti, Cu, and Zn were positively correlated with miR-122-5p (P = 0.001, 0.028 and 0.004 respectively). Ti, Cu, and Se were positively correlated with miR-3141 (P = 0.003, 0.015, and 0.031 respectively). In addition, Zn was positively correlated with miR-193b-3p (P = 0.002). Ti was negatively correlated with miR-26b-3p (P = 0.016), while Mo and miR-26b-3p were positively correlated (P = 0.042). In the mediation analysis, miR-122-5p mediated 48.0% of the association between Ti and diabetes risk. The biological mechanisms of the association are needed to be explored in further studies.
本研究旨在确定多种血浆金属水平和血浆 microRNAs（miRNAs）与糖尿病风险的关联，并进一步探讨血浆 miRNAs 对血浆金属与糖尿病风险关联的中介作用。我们通过电感耦合等离子体质谱法（ICP-MS）检测了 94 例新诊断和未经治疗的糖尿病病例和 94 例健康对照者的 23 种血浆金属水平。我们通过 microRNA 阵列筛选和 Taqman 实时 PCR 验证在相同的研究人群中检测了血浆 miRNAs。我们采用多变量逻辑回归模型探讨了血浆金属和 miRNAs 水平与糖尿病风险的关联。我们采用广义线性回归模型研究了血浆金属与血浆 miRNAs 之间的关系，并采用中介分析评估了血浆 miRNAs 对血浆金属与糖尿病风险关系的中介作用。血浆铝（Al）、钛（Ti）、铜（Cu）、锌（Zn）、硒（Se）、铷（Rb）、锶（Sr）、钡（Ba）和铊（Tl）水平与糖尿病风险升高相关，而钼（Mo）与糖尿病风险降低相关（经 FDR 多重校正后 P<0.05）。miR-122-5p 和 miR-3141 与糖尿病风险呈正相关（均 P<0.05）。Ti、Cu 和 Zn 与 miR-122-5p 呈正相关（P=0.001、0.028 和 0.004）。Ti、Cu 和 Se 与 miR-3141 呈正相关（P=0.003、0.015 和 0.031）。此外，Zn 与 miR-193b-3p 呈正相关（P=0.002）。Ti 与 miR-26b-3p 呈负相关（P=0.016），而 Mo 与 miR-26b-3p 呈正相关（P=0.042）。在中介分析中，miR-122-5p 介导了 Ti 与糖尿病风险之间 48.0%的关联。需要进一步研究来探讨这些关联的生物学机制。
