多环芳烃DNA加合物和端粒长度对胎停育的交互作用

Interaction of polycyclic aromatic hydrocarbon DNA adducts and telomere length on missed abortion

目的探讨多环芳烃DNA加合物、端粒长度改变在胎停育发生中的贡献性大小及交互作用。方法选取2019年3至12月,山西医科大学第一医院产科确诊的胎停育患者和同期同科室正常妊娠但自愿选择人工流产的孕妇为研究对象并分为病例组和对照组,采用现场问卷调查研究对象的一般情况和本次妊娠情况等,并收集流产绒毛组织,检测多环芳烃DNA(PAH-DNA)加合物含量、端粒长度(TL)。采用logistic回归模型分析胎停育的关联因素;R epiR包、mediation包分析PAH-DNA 加合物和TL对胎停育的作用和关系。结果研究对象年龄为(29.92±5.69)岁。PAH-DNA加合物M(Q1,Q3)为453.75(404.61,504.72)pg/ml。TL的M(Q1,Q3)为1.21(0.77,1.72)。病例组PAH-DNA加合物含量高于对照组(Z=-2.10,P=0.036),而TL低于对照组(Z=-4.05,P<0.001),差异有统计学意义。多因素分析显示,PAH-DNA加合物低、中、高水平(OR=3.17,95%CI:1.41~7.14;OR=2.85,95%CI:1.25~6.52;OR=2.46,95%CI:1.07~5.64)、TL长、中、短水平(OR=2.50,95%CI:1.11~5.63;OR=3.32,95%CI:1.45~7.56;OR=3.22,95%CI:1.42~7.26)均为胎停育的危险因素。PAH-DNA加合物中等水平者TL缩短是最低水平组的2.76倍,但未发现TL在PAH-DNA加合物与胎停育的关系中有中介作用。分层分析结果显示,TL水平较长(>1.21)时,PAH-DNA加合物的低、高水平与胎停育相关(均P<0.05);TL水平较短(<1.21)时,PAH-DNA加合物的中等水平与胎停育相关(P=0.025);PAH-DNA加合物水平较低时,未观察到TL对胎停育的影响;而PAH-DNA加合物水平较高时,端粒长、中和短水平与胎停育强关联(OR=7.50,95%CI:1.95~28.82;OR=6.04,95%CI:1.54~23.65;OR=9.05,95%CI:2.34~35.04)。交互作用分析显示,PAH-DNA加合物与TL交互作用归因比AP=0.72(95%CI:0.46~0.99),交互作用指数SI=5.21(95%CI:2.30~11.77)。结论 PAH-DNA加合物高水平和TL缩短可能增加胎停育的发病风险,且两者对胎停育的影响存在相加交互作用。

Objective To analyze the contribution and interaction of polycyclic aromatic hydrocarbons(PAH)-DNA adducts and changes of telomere length(TL)on missed abortion.Methods From March to December 2019,patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group.Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects.The abortion villi were collected and the content of PAH-DNA adducts and TL was detected.Logistic regression model was used to analyze the associated factors of missed abortion.R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion.Results The age of the subjects was(29.92±5.69)years old.The M(Q1,Q3)of PAH-DNA adducts was 453.75(404.61,504.72)pg/ml.The M(Q1,Q3)of TL was 1.21(0.77,1.72).The content of PAH-DNA adducts in the case group was higher than that in the control group(Z=-2.10,P=0.036),while the TL was lower than that in the control group(Z=-4.05,P<0.001).Multivariate logistic regression showed that low,medium and high levels of PAH-DNA adducts(OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64),and long,medium and short levels of TL(OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26)were all risk factors for missed abortion.The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level,and no mediating role of TL was found.The stratified analysis showed that when the TL level was longer(>1.21),the low and high levels of PAH-DNA adducts were associated with missed abortion(all P<0.05);when the TL level was shorter(<1.21),the medium level of PAH-DNA adducts was associated with abortion(P=0.025).At lower levels of PAH-DNA adducts,no effect of TL on missed abortion was observed,while,at higher levels,TL was strongly associated with missed abortion(OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04).The interaction analysis found that the AP was 0.72(95%CI:0.46-0.99),and the SI was 5.21(95%CI:2.30-11.77).Conclusion The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion,and there may be a positive additive interaction between the two factors on missed abortion.