刘秋梅, 喻国旗, 张志勇, 农春涛, 蔡建升, 徐敏, 张君玲, 许霞, 刘淑珍, 韦春梅, 覃健. 广西某金属冶炼厂工人镉暴露与认知相关基因甲基化的关联[J]. 环境与职业医学, 2021, 38(10): 1077-1082. DOI: 10.13213/j.cnki.jeom.2021.21200
引用本文: 刘秋梅, 喻国旗, 张志勇, 农春涛, 蔡建升, 徐敏, 张君玲, 许霞, 刘淑珍, 韦春梅, 覃健. 广西某金属冶炼厂工人镉暴露与认知相关基因甲基化的关联[J]. 环境与职业医学, 2021, 38(10): 1077-1082. DOI: 10.13213/j.cnki.jeom.2021.21200
LIU Qiumei, YU Guoqi, ZHANG Zhiyong, NONG Chuntao, CAI Jiansheng, XU Min, ZHANG Junling, XU Xia, LIU Shuzhen, WEI Chunmei, QIN Jian. Associations between cadmium exposure and cognition-related gene methylation of workers in a Guangxi metal smelter[J]. Journal of Environmental and Occupational Medicine, 2021, 38(10): 1077-1082. DOI: 10.13213/j.cnki.jeom.2021.21200
Citation: LIU Qiumei, YU Guoqi, ZHANG Zhiyong, NONG Chuntao, CAI Jiansheng, XU Min, ZHANG Junling, XU Xia, LIU Shuzhen, WEI Chunmei, QIN Jian. Associations between cadmium exposure and cognition-related gene methylation of workers in a Guangxi metal smelter[J]. Journal of Environmental and Occupational Medicine, 2021, 38(10): 1077-1082. DOI: 10.13213/j.cnki.jeom.2021.21200

广西某金属冶炼厂工人镉暴露与认知相关基因甲基化的关联

Associations between cadmium exposure and cognition-related gene methylation of workers in a Guangxi metal smelter

  • 摘要: 背景

    多项研究表明镉暴露与认知功能受损相关,但是关于职业镉暴露与多个认知相关基因甲基化水平的关联性研究有限。

    目的

    观察工人重金属镉职业暴露后机体认知相关的klotho(KL)、脑源性神经营养因子(BDNF)、淀粉样蛋白前体(APP)基因的甲基化水平变化,探讨镉与3个基因甲基化的关联。

    方法

    选择广西某金属冶炼厂参与2017年职业体检的职业工人作为研究对象,完成问卷调查及血样、尿样的采集。采用原子吸收光谱法测定尿镉(UCd)浓度,并经尿肌酐调整校正。根据调整后的UCd(< P25P25~P75,>P75)将研究对象分为低、中、高暴露组,将各暴露组工人按年龄、性别进行分层,采用频数匹配法从各暴露组随机抽取150例样本,应用多重PCR结合的MethylTarget技术检测APPBDNFKL基因甲基化水平。通过方差分析和Mann-Whitney U检验探索各组之间三个基因甲基化水平和CpG位点的差异,限制性立方样条分析用于探索UCd水平与基因甲基化率之间的暴露- 效应关系。

    结果

    共纳入了450名研究对象,其中男性377名(83.78%),年龄为(38.88±6.87)岁,UCd水平为2.73(1.04,5.75)μg·g-1APPBDNFKL基因平均甲基化率分别为(1.52±0.34)%、(4.55±1.08)%、(2.34±0.39)%。APP基因04片段、KL基因及其02片段的甲基化率在各暴露组间存在差异(P < 0.05);中暴露组APP基因04片段甲基化率低于低暴露组(P < 0.05),而中、高暴露组的KL基因及其02片段平均甲基化率均低于低暴露组(P < 0.05)。限制性立方样条分析的结果显示,UCd水平(lg转换)与KL基因甲基化率呈线性负相关关系(P=0.035),即随着UCd水平升高,KL基因甲基化率降低。

    结论

    镉暴露可能与KLAPP基因低甲基化率有关,KL基因甲基化水平与尿镉水平呈负相关。

     

    Abstract: Background

    Several studies have shown that cadmium exposure is related to impaired cognitive function, but there are limited studies on the association between occupational cadmium exposure and the methylation levels of cognitive-related genes.

    Objective

    This study aims to determine the methylation levels of cognition-related genes klotho (KL), brain-derived neurotrophic factor (BDNF), and amyloid protein precursor (APP) of workers after exposure to heavy metal cadmium, and explore the relationships between cadmium exposure and the methylation of the three genes.

    Methods

    The workers of a metal smelter in Guangxi who participated in 2017 an occupational physical examination were selected as study subjects and were asked to complete a questionnaire and donate blood and urine samples. The concentration of urinary cadmium (UCd) was determined by atomic absorption spectrometry, and adjusted by urinary creatinine. According to the distribution of the adjusted UCd (P25, P25-P75, >P75), the study subjects were divided into low, medium, and high exposure groups. Workers in each exposure group were stratified according to age and gender, and 150 samples were randomly selected from each exposure group by frequency matching method. Multiplex PCR combined with MethylTarget technology was employed to detect the methylation rates of APP, BDNF, and KL genes. Analysis of variance and Mann-Whitney U test were used to test the differences in the methylation levels and CpG sites of the three genes among the three groups. Restricted cubic spline (RCS) analysis was used to evaluate the exposure-effect relationship between urinary cadmium levels and gene methylation rates.

    Results

    A total of 450 workers were included in final analysis, of which 377 (83.78%) were male, with a mean age of (38.88±6.87) years, and an average UCd level of 2.73 (1.04, 5.75) μg·g-1. The average methylation rates of APP, BDNF, and KL genes were (1.52±0.34)%, (4.55±1.08)%, and (2.34±0.39)%, respectively. The methylation rates of APP gene 04 segment, KL gene, and KL gene 02 segment were different among the three exposure groups (P < 0.05). The methylation rate of APP gene 04 segment in the medium exposure group was lower than that in the low exposure group (P < 0.05); the methylation rates of KL gene and its 02 segment in the medium and high exposure groups were lower than those in the low exposure group (P < 0.05). The restricted cubic spline analysis results showed that UCd level (after lg conversion) was negatively and linearly correlated with KL gene methylation rate (P=0.035), namely KL gene methylation rate decreased with elevated UCd level.

    Conclusion

    Cadmium exposure may be related to lower methylation rates of KL and APP genes, and UCd level is negatively correlated with the methylation rate of KL gene.

     

/

返回文章
返回