全基因组DMPs/DMRs改变与健康生活方式匹配/不匹配对代谢综合征的作用及机制研究

代谢综合征（MS）是多种心脑血管病、糖尿病等慢性疾病的独立危险因素，但病因尚不明确。荷兰饥荒研究未发现其与MS的关联，但中国饥荒时间长程度重，课题组前期发现生命早期饥荒经历可增加患MS风险，但关于中国饥荒的全基因组表观遗传分析EWAS和生活方式对MS的交互作用尚未见报道。申请人利用青年基金建立的中国饥荒回顾性队列和生物样本库，开展巢式病例对照研究（112对），通过EWAS筛选出与MS关联的核心甲基化位点/区域DMPs/DMRs，同时采用匹配/不匹配模型分析其与健康生活方式的交互作用及其对MS的影响; 然后对752名研究对象进行6年后的随访，收集研究对象MS的新发情况，再次检测已筛选的DMPs/DMRs甲基化，验证其与筛选出的生活方式的交互作用。本项目有助于阐述相同饥荒暴露人群发生MS风险的个体差异，有助于MS高危人群的早期识别和早期生活方式干预，具有较好的临床和公共卫生学意义。

Metabolic syndrome (MS) is an important risk factor for cardiovascular diseases and diabetes and its etiology is not clear yet. Dutch Winter Famine was found not to be associated with MS, but Chinese Great Famine (1959-1961) was more severity and lasted much longer. Our previous study showed that infant exposed to famine increased the risk of MS, however, the interaction effects of the change of epigenome wide methylation positions and regions (DMPs/DMRs) and matched or mismatched healthy lifestyles on MS in adulthood have not been reported yet. Based on youth science project funded by National Natural Science Foundation of China, 112 subjects with MS and 112 control were selected to conduct a nested case-control study. We propose to perform epigenome-wide DNA methylation profiling for the already collected blood samples to identify DMPs and DMRs resulted from early life famine exposure, and to analysis the interaction effects of those DMPs and DMRs and healthy lifestyles with matched-mismatched model; Then we planned to do a follow-up study after six years for 752 subjects, and detected methylation level of those DMPs/DMRs to evaluate the interaction effects with healthy lifestyles, which may provide important evidence for lifestyle behavioral intervention for MS; Furthermore, the mediated effect of differentiated DMPs and DMRs on Chinese Great Famine and MS was further explored to benefit the development of novel drug and treatment targeting newly identified pathways. This study may provide clinical and public health implication to shed light on the scientific problem of individual differences in the risk of MS with the same famine exposure, and also on the early detection and early life style behavioral intervention for MS.