饮酒与多环芳烃职业暴露在焦炉工人外周血OGG1甲基化改变中的交互作用

Interaction effects of alcohol drinking and polycyclic aromatic hydrocarbons exposure on peripheral blood OGG1 methylation in coke oven workers

[目的 ]探讨饮酒与多环芳烃(PAHs)暴露在焦炉工人外周血8-羟基鸟嘌呤糖苷酶(OGG1)甲基化变化中是否存在交互作用。[方法 ]采用现况研究,选择某焦化厂焦炉工人303人作为研究对象。通过调查问卷获得工人基本信息,并采集血样和尿液。以尿中代谢物2-羟基萘(2-NAP)、2-羟基芴(2-FLU)、9-羟基菲(9-PHE)和1-羟基芘(1-OHP)作为PAHs内暴露的标志物,采用高效液相色谱-荧光检测法检测尿中4种代谢物的水平。采用焦磷酸测序法检测OGG1基因4个位点(分别距5’端第一个外显子106、121、126、142 bp)的甲基化水平。采用多因素logistic回归分析PAHs和饮酒与OGG1甲基化的关系,采用趋势检验和限制性立方样条分析其剂量反应关系。[结果]按照尿1-OHP水平的四分位数水平,将研究人群分为Q1～Q4四组。结果发现不同尿1-OHP组间,年龄分布存在差异(P=0.033);随着尿中1-OHP水平的增加,2-FLU和9-PHE均有上升的趋势。采用多元logistic回归分析,在控制了性别、年龄、受教育时间、吸烟与否、供暖方式及其他3种代谢物后,1-OHP水平、饮酒均与OGG1基因位点4高甲基化密切相关,OR值分别为2.97(95%CI:1.20～7.38)和1.67(95%CI:1.01～2.79);但未发现其他3种尿中代谢物与OGG1甲基化存在相关关系。以1-OHP水平处于Q1组且不饮酒者为参照组,1-OHP水平处于Q4组且饮酒者发生OGG1位点4高甲基化的风险是参照组的4.00倍(95%CI:1.19～13.47)。[结论]饮酒和尿1-OHP水平在焦炉工人外周血OGG1位点4的甲基化变化中存在交互作用。

[Objective] To investigate whether alcohol drinking and polycyclic aromatic hydrocarbons(PAHs) exposure have interaction effects on the peripheral blood 8-oxoguanine DNA glycosylase(OGG1) methylation in coke oven workers.[Methods] A total of 303 workers from a coking plant were recruited. General information was collected by questionnaire survey. Blood samples and urinary samples were collected to test the urinary concentrations of four PAHs metabolites, including 2-hydroxynaphthalene(2-NAP), 2-hydroxfluorene(2-FLU), 9-hydroxyphenanthren(9-PHE), and 1-hydroxypyrene(1-OHP) by high performance liquid chromatography with fluorescence detection. The methylations on four sites in OGG1(106 bp, 121 bp, 126 bp, and 142 bp from the 5’ end of the first exon) were detected by pyrosequencing. Multiple logistic regression analysis was conducted to assess the relationship of OGG1 methylation with PAHs and alcohol drinking;trend analysis and restrictive cubic spline were adopted to analyze the dose-response relationship.[Results] The participants were divided into four groups by quartiles(Q1-Q4) of urinary 1-OHP concentration. There was a significant difference in age distribution between different 1-OHP level groups(P=0.033). The levels of 2-FLU and 9-PHE showed increasing trends with higher 1-OHP levels. The results of multivariate logistic regression analysis revealed that urinary 1-OHP(OR=2.97, 95%CI: 1.20-7.38) and alcohol drinking(OR=1.67, 95%CI: 1.01-2.79) were closelyassociated with the hypermethylation on site 4 in OGG1 after adjusting for sex, age, education, smoking, heating mode, 2-NAP, 2-FLU, and 9-PHE. However, there were no significant relationships between the other three metabolites and OGG1 methylation. The coke oven workers with both urinary 1-OHP Q4 level and reported alcohol drinking had a higher risk of hypermethylation on site 4 in OGG1 than the workers with urinary 1-OHP Q1 level and without alcohol consumption(OR=4.00, 95%CI: 1.19-13.47).[Conclusion] Interactive effect of urinary 1-OHP levels and drinking on hypermethylation on site 4 in OGG1 is identified among coke oven workers.