儿童期双酚A替代物暴露对不同代谢型肥胖影响及其部分脂代谢基因甲基化水平中介作用机制研究

双酚A替代物（BPs）具有内分泌干扰作用，随着儿童肥胖率持续上升，BPs对不同代谢型肥胖的影响和机制缺乏人群研究，严重影响肥胖的精准干预和BPs暴露的健康效应评估。本课题拟采用高效液相色谱串联质谱仪法，检测2040名儿童尿液7种BPs代谢物浓度，依据BPs暴露水平分为高、中和低暴露组，开展2年随访队列研究，分析儿童BPs暴露对不同代谢型肥胖发生和进展的影响。筛选基线和随访中代谢健康型和异常型肥胖者各100名，设立2组病例组，按1:1匹配体重正常且代谢健康和代谢异常者各100名，为2组对照组，建立前瞻性巢式病例对照研究，采用基因列阵质谱分析系统检测基线和终期部分脂代谢功能基因的甲基化水平，评估甲基化在儿童BPs暴露影响不同代谢型肥胖中的表观遗传学机制。本课题研究结果将为明确BPs暴露的健康效应和阐明肥胖的环境因素致病机制提供循证依据，为制定BPs接触限值和优化肥胖精准干预策略提供新思路。

As the childhood obesity prevalence continues to rise, there is lack of study on the effects and mechanisms of bisphenol A substitute (BPs) on childhood metabolic obese phenotypes. The precise intervention to obesity and the assessment of the health effects of population BPs exposure are severely restricted. The concentrations of 7 BPs metabolites in the urine of 2040 children are detected using the High Performance Liquid Chromatography-Tandem Mass Spectrometry. According to the BPs concentrations' levels, all the children are divided into High, Middle and Low exposure groups. A 2-year follow-up cohort study is conducted to analyze the effects of population BPs exposure on the occurrence and progression of childhood metabolic obese phenotypes. Two case groups are set by screening the 100 metabolically healthy obesity and 100 metabolically unhealthy obesity children at the base line and follow-up visits. Two matched control groups with separate 100 children are selected in children with metabolically healthy normal weight and metabolically unhealthy normal weight. A prospective nested case-control study is established by detecting lipid metabolism genes methylation level at baseline and final investigation using DNA MS array analyzer. This part design is used to evaluate the epigenetic mechanism of methylation in the effects of BPs exposure on childhood metabolic obese phenotypes. The results of this study will provide an evidence-based basis for clarifying the population health effects of BPs exposure and the pathogenesis of obesity caused by environmental factors, and provide a new idea for formulating BPs exposure limits and optimizing precise intervention strategies for obesity.