铅暴露对儿童外周血基因组DNA甲基化水平的影响及其与儿童行为问题的关系

Effect of Lead Exposure on Genomic DNA Methylation in Children＇s Peripheral Blood and its Relationship with Behavioral Problems in Children

【目的】探讨铅暴露对儿童外周血基因组DNA甲基化水平的影响及高铅血症与儿童行为问题的关系。【方法】选取2016年1～6月在本院儿童保健所门诊健康体检筛查出的80例血铅水平≥100μg／L的儿童为观察组，同期选择于本院健康体检的80例同年龄、同性别、血铅水平〈100μg／L儿童为对照组。采用Methyflash^TM总体DNA甲基化试剂盒检测外周血单个核细胞基因组DNA总体甲基化水平，采用Conner＇s儿童行为问卷（家长量表）对儿童行为问题进行筛查，并分析DNA甲基化水平与各行为因子评分之间的相关性。【结果】观察组行为问题检出率明显高于对照组（P〈0．05），Conner’s量表评分中学习问题、冲动一多动、多动指数评分显著高于对照组（P〈0．05）。外周血单个核细胞基因组DNA总体甲基化水平明显降低，差异有统计学意义（P=0．0261），DNA总体甲基化水平与血铅水平呈负相关（P〈0．001），与冲动一多动评分呈负相关（P=0．0436）。【结论】高铅血症会增加儿童行为问题发生率，突出表现为学习问题及冲动、多动行为，儿童外周血基因组DNA总体甲基化水平受血铅影响，且与儿童多动行为问题呈负相关。

[Objective]To investigate the effect of lead exposure on genomic DNA methylation in children＇s peripheral blood and the relationship between hyperleadinemia and behavioral problems in children.[Methods] From January to June 2016, 80 children with blood lead level ≥ 100 μg/L were selected as observation group and 80 healthy children in health examination of the same age, same sex and blood lead level 〈 100 μg/L as control group. The total methylation level of genomic DNA in peripheral blood mononuclear cells was detected by the Methyflash^TM Total DNA Methylation Kit. Children＇s behavioral problems were screened by Conner＇s Children behavior questionnaire （parent scale）, and the correlation between DNA methylation level and behaw ioral factor scores was analyzed.[Results]The detection rate of behavioral problems in the observation group ＂was significantly higher than that in the control group （ P 〈0.05）. The scores of learning problems, impulsive hyperactivity and hyperactivity index in Conner＇s scale were significantly higher than those in control group （ P 〈0.05）. The total methylation level of genomic DNA in peripheral blood mononuclear cells was significantly decreased, the difference was statistically significant （ P = 0.0261）. There was a negative correlation between total methylation level and blood lead level （ P 〈0.001）, and a negative correlation between total methylation level and impulse hyperactivity score （ P 〈0.0436）.[Conclusion]Hyperleadinemia can increase the incidence of behavioral problems in children, especially learning problems and impulses, hyperactivity behavior. The total methylation level of genomic DNA in children＇s peripheral blood is affected by blood lead, and it is negatively correlated with children＇s hyperactivity behavior problems.