目前关于暴露于多种污染物组合的表观遗传影响的研究是有限的。本研究旨在识别与多种污染物暴露相关的 DNA 甲基化探针，作为早期效应标记，以及作为人群易感性替代指标的单核苷酸多态性 (SNP)。该调查涉及 11 种重金属（钒、砷、汞、镉、铬、镍、铅、锰、铜、锶、铊）、多环芳烃 (PAH)（1-羟基芘）、基因组的尿液暴露生物标志物分析对所有研究参与者进行全 DNA 甲基化测序和 SNP 阵列。这些数据与代谢组学信息相结合，并在基于相对于复合体的家庭住址的邻近性的社区层面和基于暴露生物标志物浓度的个体层面进行分析。在社区层面，鉴定了 67 个与暴露相关的 CpG 探针，同时在个体水平上，70 个 CpG 探针与尿砷浓度相关，2 个与汞相关，46 个与钒相关。这些探针被注释为与癌症和慢性肾病有关的基因。加权分位数和回归分析显示，钒、汞和1-羟基芘对cg08238319低甲基化贡献最大。 cg08238319 被注释为芳烃受体阻遏物 (AHRR) 基因，AHRR 低甲基化与肺癌风险升高相关。 AHRR 进一步与苯丙氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢失调以及氧化应激加剧有关。此外，与暴露相关的 CpG 探针相对应的三个 SNP（rs11085020、rs199442 和 rs10947050）与多种重金属和 PAH 暴露表现出显着的相互作用，并且与癌症进展和呼吸系统疾病有关。我们的研究结果强调了 AHRR 的关键作用基因-环境相互作用中的甲基化，并突出显示可能作为暴露于多种重金属和 PAH 的地区人群易感性指标的 SNP。© 2024。作者。

Current research on the epigenetic repercussions of exposure to a combination of pollutants is limited. This study aims to discern DNA methylation probes associated with exposure to multiple pollutants, serving as early effect markers, and single-nucleotide polymorphisms (SNPs) as surrogate indicators for population susceptibility. The investigation involved the analysis of urine exposure biomarkers for 11 heavy metals (vanadium, arsenic, mercury, cadmium, chromium, nickel, lead, manganese, copper, strontium, thallium), polycyclic aromatic hydrocarbon (PAHs) (1-hydroxypyrene), genome-wide DNA methylation sequencing, and SNPs array on all study participants. The data were integrated with metabolomics information and analyzed both at a community level based on proximity to home addresses relative to the complex and at an individual level based on exposure biomarker concentrations.On a community level, 67 exposure-related CpG probes were identified, while 70 CpG probes were associated with urine arsenic concentration, 2 with mercury, and 46 with vanadium on an individual level. These probes were annotated to genes implicated in cancers and chronic kidney disease. Weighted quantile sum regression analysis revealed that vanadium, mercury, and 1-hydroxypyrene contributed the most to cg08238319 hypomethylation. cg08238319 is annotated to the aryl hydrocarbon receptor repressor (AHRR) gene, and AHRR hypomethylation was correlated with an elevated risk of lung cancer. AHRR was further linked to deregulations in phenylalanine metabolism, alanine, aspartate, and glutamate metabolism, along with heightened oxidative stress. Additionally, three SNPs (rs11085020, rs199442, and rs10947050) corresponding to exposure-related CpG probes exhibited significant interaction effects with multiple heavy metals and PAHs exposure, and have been implicated in cancer progression and respiratory diseases.Our findings underscore the pivotal role of AHRR methylation in gene-environment interactions and highlight SNPs that could potentially serve as indicators of population susceptibility in regions exposed to multiple heavy metals and PAHs.© 2024. The Author(s).