镉相关 DNA 甲基化的全基因组表观遗传学观点及其在镉与脂质水平和血脂异常风险关联中的中介作用。

Epigenome-wide perspective of cadmium-associated DNA methylation and its mediation role in the associations of cadmium with lipid levels and dyslipidemia risk.

机构信息

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, Hubei, China; Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, 530021, China.

出版信息

Food Chem Toxicol. 2024 Feb;184:114409. doi: 10.1016/j.fct.2023.114409. Epub 2023 Dec 20.

DOI:10.1016/j.fct.2023.114409

PMID:38128686

Abstract

BACKGROUND

Studies demonstrated the associations of cadmium (Cd) with lipid levels and dyslipidemia risk, but the mechanisms involved need further exploration.

OBJECTIVES

We aimed to explore the role of DNA methylation (DNAM) in the relationship of Cd with lipid levels and dyslipidemia risk.

METHODS

Urinary cadmium levels (UCd) were measured by inductively coupled plasma mass spectrometry, serum high-density lipoprotein (HDL), total cholesterol, triglyceride, and low-density lipoprotein were measured with kits, and DNAM was measured using the Infinium MethylationEPIC BeadChip. Robust linear regressions were conducted for epigenome-wide association study. Multivariate linear and logistic regressions were performed to explore the associations of UCd with lipid levels and dyslipidemia risk, respectively. Mediation analyses were conducted to explore potential mediating role of DNAM in the associations of Cd with lipid levels and dyslipidemia risk.

RESULTS

UCd was negatively associated with HDL levels (p = 0.01) and positively associated with dyslipidemia (p < 0.01). There were 92/11 DMPs/DMRs (FDR<0.05) associated with UCd. Cd-associated DNAM and pathways were connected with cardiometabolic diseases and immunity. Cg07829377 (LINC01060) mediated 42.05%/22.88% of the UCd-HDL/UCd-dyslipidemia associations (p = 0.02 and 0.01, respectively).

CONCLUSIONS

Cadmium caused site-specific DNAM alterations and the associations of UCd with lipid levels and dyslipidemia risk may be partially mediated by DNAM.

摘要

背景

研究表明，镉（Cd）与血脂水平和血脂异常风险有关，但相关机制仍需进一步探讨。

目的

本研究旨在探讨 DNA 甲基化（DNAM）在 Cd 与血脂水平和血脂异常风险关系中的作用。

方法

采用电感耦合等离子体质谱法测定尿镉（UCd）水平，试剂盒测定血清高密度脂蛋白（HDL）、总胆固醇、甘油三酯和低密度脂蛋白，采用 Infinium MethylationEPIC BeadChip 测定 DNAM。进行全基因组关联研究的稳健线性回归。多元线性和逻辑回归分别用于探讨 UCd 与血脂水平和血脂异常风险的关系。中介分析用于探讨 Cd 与血脂水平和血脂异常风险关系中 DNAM 的潜在中介作用。

结果

UCd 与 HDL 水平呈负相关（p=0.01），与血脂异常呈正相关（p<0.01）。有 92/11 个 DMPs/DMRs（FDR<0.05）与 UCd 相关。Cd 相关的 DNAM 和途径与心脏代谢疾病和免疫有关。Cg07829377（LINC01060）介导了 42.05%/22.88%的 UCd-HDL/UCd-血脂异常关联（p=0.02 和 0.01）。