外周血线粒体DNA拷贝数在焦化厂工人多环芳烃暴露与血脂水平关系中的中介效应分析

Mitochondrial DNA copy number in peripheral blood mediates the association between polycyclic aromatic hydrocarbons exposure and blood lipid levels among coke oven plant workers

目的探讨外周血线粒体DNA拷贝数(mitochondrial DNA copy number,mtDNAcn)在焦化厂工人多环芳烃(polycyclic aromatic hydrocarbons,PAHs)暴露与血脂水平关系中的中介作用。方法采用高效液相色谱-质谱联用(high performance liquid chromatography with tandem mass spectrometry,HPLC-MS/MS)检测661名焦化厂工人尿中11种PAHs羟基代谢物(polycyclic aromatic hydrocarbons hydroxy metabolites,OH-PAHs)。采用反转录聚合酶链反应(reverse transcriptionpolymerase chain reaction,RT-PCR)技术检测外周血mtDNAcn。应用广义线性回归分析PAHs暴露与外周血mtDNAcn以及血脂指标的剂量-效应关系,应用中介效应分析mtDNAcn在PAHs暴露与血脂水平关系中的中介作用。结果按照尿OH-PAHs的三分位数(tertile,T),将研究人群分为T1~T3三组。广义线性回归结果显示,校正混杂因素后,随着2-羟基萘(2-hydroxynaphthalene,2-OHNAP)和2-羟基菲(2-hydroxyphenanthrene,2-OHPHE)的升高,mtDNAcn下降(β=-0.240,95%CI:-0.400~-0.081;β=-0.236,95%CI:-0.412~-0.059);T3组与T1组相比,2-OHPHE浓度每增加一个单位,TC水平增加0.335(β=0.335,95%CI:0.084~0.587);2-羟基芴(2-hydroxyfluorene,2-OHFLU)浓度每增加一个单位,TG水平增加0.357(β=0.357,95%CI:0.102~0.612);1-羟基萘(1-hydroxynaphthalene,1-OHNAP)T2组和T3组与T1组相比浓度每增加一个单位,HDL-C水平分别下降0.232和0.615(β=-0.232,95%CI:-0.430~-0.035;β=-0.615,95%CI:-0.858~-0.373)。中介分析结果显示,mtDNAcn在PAHs暴露与血脂水平关系中起到部分中介作用,中介比例为12.61%。结论焦化厂工人PAHs暴露可能通过外周血mtDNAcn下降从而对血脂产生不利影响。

Objective To investigate the mediating role of mitochondrial DNA copy number(mtDNAcn)in the association between exposure to polycyclic aromatic hydrocarbons(PAHs)and blood lipid levels in coke-oven plant workers.Methods Eleven urine biomarkers of PAHs exposure of 661 coking plant workers were determined by high performance liquid chromatography with tandem mass spectrometry(HPLC-MS/MS).Relative mtDNAcn was measured based on RT-PCR.The dose-effect relationship between PAHs and mtDNAcn in peripheral blood and blood lipid parameters by the generalized linear regression model,and mediating effect analysis was used to analyze the role of mtDNAcn in PAHs exposure and abnormal blood lipid levels.Results The participants were divided into three groups by tertiles(T1-T3)of urinary PAHs hydroxy metabolites concentration.The results of generalized linear regression showed that mtDNAcn decreased with the increase of 2-hydroxynaphthalene(2-OHNAP)and 2-hydroxyphenanthrene(2-OHPHE)after adjusting for confounding factors(β=-0.240,95%CI:-0.400--0.081;β=-0.236,95%CI:-0.412--0.059),and compared with individuals with the lowest levels of urinary 2-OHPHE,those in the highest tertile subgroups of 2-OHPHE had increased TC levels(β=0.335,95%CI:0.084-0.587).Compared with individuals with the lowest levels of urinary 2-hydroxyfluorene(2-OHFLU)those in the highest tertile subgroups of 2-OHFLU had increased TG levels 0.357(β=0.357,95%CI:0.102-0.612).Compared with individuals with the lowest levels of urinary 1-hydroxynaphthalene(1-OHNAP)those in the middle of the highest tertile subgroups of 1-OHNAP had decreased HDL-C levels(β=-0.232,95%CI:-0.430--0.035,β=-0.615,95%CI:-0.858--0.373).The results of mediating effect analysis showed that the effect of 2-OHPHE on TC levels may be mediated by the reduction of mtDNAcn,with a mediation ratio of 12.61%.Conclusions PAHs exposure in coke-oven plant workers may adversely affect blood lipids by decreasing mtDNAcn in peripheral blood.