Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
Environ Health Perspect. 2022 Aug;130(8):87009. doi: 10.1289/EHP10602. Epub 2022 Aug 29.
Exposure to heavy metals has been reported to be associated with multiple diseases. However, direct associations and potential mechanisms of heavy metals with physical disability remain unclear.
We aimed to quantify associations of heavy metals with physical disability and further explore the potential mechanisms of DNA methylation on the genome scale.
A cross-sectional study of 4,391 older adults was conducted and activities of daily living (ADL) disability were identified using a 14-item scale questionnaire including basic and instrumental activities to assess the presence of disability (yes or no) rated on a scale of dependence. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated to quantify associations between heavy metals and ADL disability prevalence using multivariate logistic regression and Bayesian kernel machine regression (BKMR) models. Whole blood-derived DNA methylation was measured using the HumanMethylationEPIC BeadChip array. An ADL disability-related epigenome-wide DNA methylation association study (EWAS) was performed among 212 sex-matched ADL disability cases and controls, and mediation analysis was further applied to explore potential mediators of DNA methylation.
Each 1-standard deviation (SD) higher difference in -transformed manganese, copper, arsenic, and cadmium level was significantly associated with a 14% (95% CI: 1.05, 1.24), 16% (95% CI:1.07, 1.26), 22% (95% CI:1.13, 1.33), and 15% (95% CI:1.06, 1.26) higher odds of ADL disability, which remained significant in the multiple-metal and BKMR models. A total of 85 differential DNA methylation sites were identified to be associated with ADL disability prevalence, among which methylation level at cg220000984 and cg23012519 (annotated to and ) mediated 31.0% and 31.2% of manganese-associated ADL disability prevalence, cg06723863 (annotated to ) mediated 32.4% of copper-associated ADL disability prevalence, cg24433124 (nearest to ) mediated 15.8% of arsenic-associated ADL disability prevalence, and cg07905190 and cg17485717 (annotated to and ) mediated 21.5% and 30.5% of cadmium-associated ADL disability prevalence (all ).
Our findings suggested that heavy metals contributed to higher prevalence of ADL disability and that locus-specific DNA methylation are partial mediators, providing potential biomarkers for further cellular mechanism studies. https://doi.org/10.1289/EHP10602.
据报道，重金属暴露与多种疾病有关。然而，重金属与身体残疾的直接关联和潜在机制仍不清楚。
我们旨在量化重金属与身体残疾的关联，并进一步探索全基因组范围内 DNA 甲基化的潜在机制。
对 4391 名老年人进行了一项横断面研究，使用包括基本和工具性活动的 14 项日常生活活动（ADL）残疾量表问卷来确定 ADL 残疾，并使用依赖程度评分来评估残疾的存在（是或否）。使用多变量逻辑回归和贝叶斯核机器回归（BKMR）模型，使用比值比（OR）和 95%置信区间（CI）来估计重金属与 ADL 残疾患病率之间的关联。使用 HumanMethylationEPIC BeadChip 阵列测量全血衍生的 DNA 甲基化。在 212 名性别匹配的 ADL 残疾病例和对照中进行了与 ADL 残疾相关的全基因组 DNA 甲基化关联研究（EWAS），并进一步应用中介分析来探索 DNA 甲基化的潜在中介。
我们的研究结果表明，重金属会导致 ADL 残疾的患病率增加，而特定基因座的 DNA 甲基化是部分中介，为进一步的细胞机制研究提供了潜在的生物标志物。
